Oligomerisation products of alpha-pinene and beta-pinene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 December 2013 - 25 February 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study performed according to OECD test guideline No. 423 and in compliance with GLP.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

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:

French GLP Compliance Programme for chemical products (inspected on 03-04 June 2013 / signed on 13 September 2013)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

alpha-pinene and beta-pinene dimers

IUPAC Name:

alpha-pinene and beta-pinene dimers

Constituent 2

Reference substance name:

alpha-pinene and beta-pinene trimers

IUPAC Name:

alpha-pinene and beta-pinene trimers

Constituent 3

Reference substance name:

alpha-pinene and beta-pinene tetramers

IUPAC Name:

alpha-pinene and beta-pinene tetramers

Test material form:

liquid: viscous

Details on test material:

Batch No. 1302SI
Purity: 100% (UVCB substance)
Name of the test item (as cited in the study report): TERPENIC OLIGOMERS
Physical state: yellow viscous liquid
Storage Conditions: +2°C to +8°C, under nitrogen and protected from light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

(SPF Caw)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS (53940 Le Genest St Isle – France)
- Females (if applicable) nulliparous and non-pregnant: Not specified
- Age at study initiation: 8 weeks old
- Weight at study initiation: 183 - 197 g
- Fasting period before study: food was removed at D-1 and then redistributed 4 hours after the test item administration.
- Housing: housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry.
- Diet (e.g. ad libitum): foodstuff (SAFE, A04), ad libitum
- Water (e.g. ad libitum): drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 25 °C
- Humidity (%): 39 - 59%
- Air changes (per hr): ca. 13 changes per hour
- Photoperiod (hrs dark / hrs light): 12h light / 12h darkness

IN-LIFE DATES: From: 14 January 2014 To: 29 January 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.14 mL/kg body weight (corresponding to 2 g/kg, according to the calculated density)

DOSAGE PREPARATION (if unusual): The test item was used as supplied in this study.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The experimental protocol was established according to the official method as defined in the OECD guideline No. 423 dated December 17th, 2001 and the test method B.1tris of the Council regulation No. 440/2008.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females/dose (3 females for the Step 1 and 3 females for the Step 2)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations: Systematic examinations were carried out daily to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item. Observations and a mortality report were then carried out every day for 14 days.
- Frequency of weighing: D0 (just before administering the test item) then on D2, D7, and D14.
- Necropsy of survivors performed: Yes; On D14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels.
- Other examinations performed: Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. Those presenting macroscopic anomalies can be removed and preserved in view to microscopic examinations.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

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.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs related to the administration of the test item were observed during the study.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal any treatment related changes.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of the test substance, Terpenic Oligomers, is higher than 2000 mg/kg bw in female rats. In accordance with OECD Guideline No. 423, the LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat. Therefore, the test substance, Terpenic Oligomers, is not classified for acute oral toxicity according to;Regulation (EC) No 1272/2008 (CLP) and according to the GHS Regulation.

Executive summary:

An acute oral toxicity study was performed according to OECD Guideline 423 and in compliance with GLP.

One group of three fasted female SPF Caw (SD) rats received a single oral gavage dose of the test substance at a dose level of 2000 mg/kg bw. As results at this dose level indicated the acute lethal oral dose of the test substance to be greater than 2000 mg/kg bw, in compliance with the study guidelines, a further group of three fasted females was similarly administered a dose of 2000 mg/kg bw to complete the study. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

There were no deaths during the study. No clinical signs related to the administration of the test item were observed during the study and the body weight evolution of the animals remained normal throughout the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Therefore, the oral LD50 of the test substance, Terpenic Oligomers, is higher than 2000 mg/kg bw in female rats. In accordance with OECD Guideline No. 423, the LD50 cut-off of the test item may be considered to be higher than 5000 mg/kg body weight by oral route in the rat. Therefore, the test substance, Terpenic Oligomers, is not classified for acute oral toxicity according to Regulation (EC) No 1272/2008 (CLP) and according to the GHS Regulation.

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