Storax (balsam)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 May 2017 - 01 Jun 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF), November 2000.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Storax (balsam)

EC Number:

232-458-4

EC Name:

Storax (balsam)

Cas Number:

8046-19-3

Molecular formula:

Not applicable, UVCB - NCS

IUPAC Name:

Storax (balsam)

Test material form:

other: liquid

Details on test material:

CAS : 8046-19-3 EINECS : 232-458-4
- Name of test material (as cited in study report): STYRAX RESINOID OIL
- Test Facility test item number: 208399/A
- Appearance: Orange viscous liquid
- Substance type: pure substance
- Physical state: liquid
- Analytical purity: 100%

Specific details on test material used for the study:

Identification: Styrax resinoid oil
Test Facility test item number: 208399/A
Appearance: Orange viscous liquid

Purity/Composition: 100%
Test item storage: At room temperature
Stable under storage conditions until: 02 February 2019

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 11 weeks old
- Weight at study initiation: 194 to 230 g
- Housing: group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany)
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study.
- Water: Municipal tap-water was freely available to each animal via water bottles.
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Acclimation period:The animals were allowed to acclimate to the Test Facility toxicology accommodation for at least 5 days before the commencement of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 22
- Humidity (%): 43 to 64
- Air changes (per hr): Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Trial preparations were performed at the Test Facility to select the suitable vehicle and to establish a suitable formulation procedure
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements. The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing. Adjustment was made for specific gravity of the vehicle and test item. No correction was made for the purity/composition of the test item.

CLASS METHOD
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day.
- Necropsy of survivors performed: yes, All moribund animals and animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded
- Other examinations performed:
Clinical Observations: Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate). Signs were graded for severity and the maximum grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2), severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or absence (grade 0) was scored.

Body Weights: Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

Hunched posture and piloerection were noted for all animals on Day 1. Scabs on the right shoulder were noted for one animal on Day 15 only, since this was an incidental finding on one day and in one animal only it was considered not indicative of systemic toxicity.

Body weight:

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Gross pathology:

Ectopic splenic tissue was found in one animal at macroscopic post mortem examination, this finding is occasionally seen in rats of this age and strain and was therefore considered not toxicologically significant. Macroscopic post mortem examination of the other animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of Styrax resinoid oil in Wistar rats was established to exceed 2000 mg/kg body weight. In conclusion, Styrax resinoid oil does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

The potential acute oral toxicity of Styrax resinoid oil was investigated with an Acute Toxic Class study, according to OECDTG 423.Styrax resinoid oil was administered by oral gavage to two consecutive groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Hunched posture and piloerection were noted for all animals on Day 1. The body weight gain shown by the animals over the study period was considered to be normal. Macroscopic post mortem examination of the animals at termination did not reveal any test item related abnormalities. The oral LD50 value of Styrax resinoid oil in Wistar rats was established to exceed 2000 mg/ kg body weight.

In conclusion, Styrax resinoid oil does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).