Reaction mass of 4-isopropylidene-1-methylcyclohexene and 1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane and 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09-24 May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline 423 without any deviation

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:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 4-isopropylidene-1-methylcyclohexene and 1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane and 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane

EC Number:

938-945-4

Molecular formula:

Not applicable

IUPAC Name:

Reaction mass of 4-isopropylidene-1-methylcyclohexene and 1-isopropyl-4-methyl-7-oxabicyclo[2.2.1]heptane and 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane

Test material form:

gas under pressure: refrigerated liquefied gas

Details on test material:

- Name of test material (as cited in study report): Terpinolene multiconstituent
- Physical state: Yellow liquid
- Analytical purity: 66.9 %
- Composition of test material (%): Terpineols (4.4 %), alpha pinene (1.1 %), alpha fenchene (0.2 %), camphene (1.0 %), alpha phellandrene (0.5 %), alpha terpinene (2.7 %), cineol 1.4 (20.5 %), d-limonene (9.1 %), l-limonene (9.1 %), beta phellandrene (0.2 %), paracymene (0.7 %), cineol 1.8 (14.6 %), gamma terpinene (3.6%), terpinolene (31.8 %) and others (0.5 %)
- Lot/batch No.: 123238
- Purity test date: 17 October 2011
- Date of receipt: 16 April 2012
- Expiration date of the lot/batch: 29 September 2012
- Storage condition of test material: Stored at 6 ± 3 °C in darkness

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 or 9 weeks
- Weight at study initiation: 190-213 g
- Housing: 3 animals/cage
- Diet: Food (M20, SDS), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-70 %
- Air changes: At least 10 cycles per hour
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME ADMINISTERED: 2.28 mL/kg bw (corresponding to 2000 mg/kg bw, according to the density of 0.877)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

- Step 1: 3 females
- Step 2: 3 females

Control animals:

other: Study no. TAO-2012-001 (no treatment related changes were observed)

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed for any behavioural or toxic effects at 30 minutes, 1, 3, 4, 24 and 48 h after administration of the item and thereafter once a day until Day 14.
Bodyweight was recorded on Days 0 (prior to dosing), 2, 7 and 14.
- Necropsy of survivors performed: Yes; On Day 14, the animals were anaesthetised with sodium pentobarbital and then administered sodium pentobarbital up to a lethal dose and were subjected to a macroscopic examination.

Statistics:

None

Results and discussion

Preliminary study:

Not Applicable

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality and no clinical signs were observed.

Mortality:

- No mortality was observed.

Clinical signs:

other: - Decrease in spontaneous activity (4/6), piloerection (3/6), and mydriasis (1/6) were noted during the first hours of the test. - Animals recovered a normal behaviour between 24 and 48 h post dose.

Gross pathology:

- No macroscopic abnormalities were observed at necropsy.

Other findings:

None

Any other information on results incl. tables

Table 7.2.1/1: Body weight and weight gain in grams

Female rats	D0	D2	D2-D0	D7	D7-D0	D14	D14-D0
Rf 0056	213	214	1	229	16	248	35
Rf 0057	201	200	-1	225	24	237	36
Rf 0058	208	208	0	225	17	238	30
Rf 0117	190	195	5	215	25	228	38
Rf 0118	194	201	7	222	28	243	49
Rf 0119	205	213	8	240	35	259	54
Mean	201.8	205.2	3.3	226.0	24.2	242.2	40.3
Standard deviation	8.7	7.7	3.8	8.3	7.1	10.6	9.2

D: Day

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 Terpinolene multiconstituent is higher than 2000 mg/kg bw in female rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, 6 Sprague Dawley female rats were given a single oral (gavage) dose of Terpinolene multiconstituent 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.

No mortality was observed. Decrease in spontaneous activity, piloerection and mydriasis were noted during the first hours of the test, however animals recovered a normal behaviour between 24 and 48 h post dose. Lower body weight gain was noted in treated animals on Day 2 compared to the historical control group. No macroscopic abnormalities were observed at necropsy. In this study, the oral LD50 of Terpinolene multiconstituent was considired to be higher than 2000 mg/kg bw in female rats.

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