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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-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
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

Constituent 1
Chemical structure
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:
- 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.
Body weight:
- Lower body weight gain was noted in treated animals on Day 2 compared to the historical control group: +2 % versus +l0 %, respectively.
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).

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