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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
08 January-12 February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD Guideline 420 without any deviation.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on 10 July 2012/ signed on 30 November 2012)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Pinus Pinaster oil
- Physical state: Extremely pale yellow liquid
- Analytical purity: Conforms to standard
- Purity test date: 12 December 2013
- Lot/batch No.: 1012/1
- Manufacturing date of the lot/batch: 10 October 2012
- Expiration date of the lot/batch: 10 October 2014
- Storage condition of test material: Stored at room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 147-156 g (main study)
- Fasting period before study: Animals were fasted overnight before treatment and food was given approximately 3-4 h after dosing.
- Housing: Animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: 2014C Teklad Global Rodent diet (Harlan Laboratories UK Ltd., 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/h
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL (for 300 mg/kg bw)
- Justification for choice of vehicle: Arachis oil BP was used because the test item was not dissolved/suspended in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw for 300 mg/kg bw dose; 2.31 mL/kg bw for 2000 mg/kg bw dose (specific gravity – 0.869)

DOSAGE PREPARATION (if unusual): Test item at 2000 mg/kg bw dose was used as concentrate. For 300 mg/kg bw dose, test item was freshly prepared as solution in arachis oil BP. The test item was formulated within 2 h of dosing and assumed that the formulation was stable for this duration..
Doses:
- Sighting study: 300 and 2000 mg/kg bw
- Main study: 2000 mg/kg bw
No. of animals per sex per dose:
- Sighting study: 1 female/dose (300 and 2000 mg/kg bw)
- Main study: 4 females (2000 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Each animal was checked for morbidity and mortality twice daily for 14 days. Clinical observations were made 0.5, 1, 2 and 4 h after dosing and then daily for 14 days.
Body weight: Body weight of each animal was recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes; on completion of the observation period, animals were killed by cervical dislocation and macroscopic examination was performed.
Statistics:
None

Results and discussion

Preliminary study:
- No mortality and systemic toxicity were observed in the initial animal treated at 300 and 2000 mg/kg bw dose
- Animal showed expected gains in body weight over the observation period
- No abnormality was noted at necropsy
Effect levels
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 was observed
Clinical signs:
- Hunched posture and increased salivation were observed in the additional four animals treated at 2000 mg/kg bw and one of these animals showed noisy respiration.
Body weight:
- All animals showed expected gains in body weight over the observation period
Gross pathology:
- 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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the oral LD50 for Pinus Pinaster oil is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Directive 67/548/EEC and the Regulation (EC) N° 1272-2008.
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 420 and in compliance with GLP, a group of five female Wistar (RccHan™:WIST) rats were given a single oral dose of the test item Pinus Pinaster oil at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination. Before the main test, a sighting test was also conducted on 1 female rat/dose at 300 and 2000 mg/kg bw and animals were observed for 14 days. As no mortality occurred, the test item was administered to four additional animals at the dose level of 2000 mg/kg bw (main test).

No mortality was observed. No sign of systemic toxicity was observed in the initial animal treated at 300 and 2000 mg/kg bw dose level (sighting study). Signs of systemic toxicity observed in animals of the main study treated at a dose level of 2000 mg/kg bw were hunched posture, increased salivation and noisy respiration. All animals showed expected gains in body weight. No abnormalities were noted at necropsy. In this study, the oral LD50 of Pinus Pinaster oil was considered to be higher than 2000 mg/kg bw in female rats.

Under the test conditions, the oral LD50 for Pinus Pinaster oil is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Directive 67/548/EEC and the Regulation (EC) N° 1272-2008.