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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 - 23 May 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to OECD Guideline 402 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 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute 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:
male/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: Males: 7 weeks; females: 8 weeks
- Weight at study initiation: Males: 212-227 g; females: 187-216 g
- Housing: Animals were housed in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid; During the treatment and up to Day 8, the animals were kept in individual cages and were put into their cage by group of 5 on Day 9.
- Diet: Food (M20, SDS), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: Approximately 10-15 changes/h
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 h before the treatment, fur was removed from the dorsal area of the trunk of the test animals by clipping.

TEST SITE
- Area of exposure: Dorsal area of the trunk
- % coverage: Approximately 10 % of the body surface area
- Type of wrap if used: Test material was applied by topical application, under porous gauze dressing.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Dose volume: 2.28 mL/kg bw (corresponding to 2000 mg/kg bw according to the density of 0.877)
- Constant volume or concentration used: Yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: Study no.: TAD-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 on vital functions 1, 3, 5 and 24 h after administration of the test 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:
male/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:
- No systemic clinical signs related to the administration of the test item was observed.
- Cutaneous reactions (erythema, dryness and scab) were noted on the treated area of three females (3/5) and three males (3/5), 24 or 48 h after the test item application and were totally reversible on Day 9 in all animals.
Body weight:
- Body weight gain of the treated animals was not affected by the test item.
Gross pathology:
- No macroscopic abnormalities were observed at necropsy.
Other findings:
None

Any other information on results incl. tables

Table 7.2.3/1: Body weight and weight gain in grams

Male rats

D0

D2

D2-D0

D7

D7-D0

D14

D14-D0

Rm 0084

226

228

2

261

35

312

86

Rm 0085

221

225

4

262

41

312

91

Rm 0086

212

214

2

259

47

309

97

Rm 0087

217

216

-1

267

50

337

120

Rm 0088

227

236

9

285

58

344

117

Mean

220.6

223.8

3.2

266.8

46.2

322.8

102.2

Standard deviation

6.3

9.0

3.7

10.6

8.8

16.4

15.4

Female rats

D0

D2

D2-D0

D7

D7-D0

D14

D14-D0

Rf 0089

187

182

-5

200

13

218

31

Rf 0090

199

206

7

227

28

246

47

Rf 0091

200

201

1

234

34

248

48

Rf 0092

203

196

-7

220

17

241

38

Rf 0093

216

209

-7

236

20

250

34

Mean

201.0

198.8

-2.2

223.4

22.4

240.6

39.6

Standard deviation

10.4

10.6

6.1

14.5

8.5

13.1

7.6

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 acute dermal LD50 of Terpinolene multiconstituent is higher than 2000 mg/kg bw in 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 dermal toxicity study (limit test) performed according to OECD Guideline 402 and in compliance with GLP, Sprague Dawley rats (5/sex/dose) were given a single dermal application of Terpinolene multiconstituent at 2000 mg/kg bw. The test item was placed directly on dorsal area of the skin representing approximately 10 % of the total body surface of the animals. The test site was then covered by a semiocclusive dressing for 24 h. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality and no clinical signs were observed during the study. Cutaneous reactions (erythema, dryness and scab) were noted on the treated area of three females and three males, 24 or 48 h after the test item application and were totally reversible on Day 9 in all animals. Body weight gain of the treated animals was not affected by the test item. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 of Terpinolene multiconstituent was considered to be higher than 2000 mg/kg bw in rats.

Under the test conditions, the acute dermal LD50 of Terpinolene multiconstituent is higher than 2000 mg/kg bw in 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).