6,6-dimethoxy-2,5,5-trimethylhex-2-ene

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2002-03-18 to 2002-04-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

6,6-dimethoxy-2,5,5-trimethylhex-2-ene

EC Number:

266-885-2

EC Name:

6,6-dimethoxy-2,5,5-trimethylhex-2-ene

Cas Number:

67674-46-8

Molecular formula:

C11H22O2

IUPAC Name:

6,6-dimethoxy-2,5,5-trimethylhex-2-ene

impurity 1

Reference substance name:

Unknown impurities

Molecular formula:

Unknown

IUPAC Name:

Unknown impurities

Test material form:

liquid

Specific details on test material used for the study:

Test article: HR 02/197007
Chemical name: 2-Hexene, 6,6-dimethoxy-2,5,5-trimethyl-
CAS No.: 0067674-46-8
Test article name for report: HR 02/197007
Batch No.: 000003
Test concentration (v/v): 100 %, 50 %, 25 %, 10 %, 1 %, 0 % (vehicle)
Description of test article: colourless to slight yellowish, liquid
Arrival of test article: 27th February 2002
Expiration date: 31s t Dec. 2002
Storage of test article: dark, cool and dry

Test animals

Species:

rabbit

Strain:

other: SPF albino Chbb:HM(SPF) - Littlerussian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BI Pharma KG, Biberach, Germany
- Weight at study initiation: between 2.7 and 2.9 kg bw
- Housing: kept in individual box provided with filtered air
- Acclimation period: 7 days
- Diet (e.g. ad libitum): Altromin 2123 supplied from Altromin, D-32791 Lage, Germany, ad libitum
- Water (e.g. ad libitum): bottles with domestic quality drinking water acidified with hydrochloric acid to pH2.5, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 17 and 23
- Humidity (%): between 40 and 70
- Air changes (per hr): at least 10 cycles
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: ethanol/diethylphthalat 1:1

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted, 50%, 25%, 10%, 1%, 0% (vehicle)

Duration of treatment / exposure:

4 h

Observation period:

21 days

Number of animals:

4 females

Details on study design:

TEST SITE
- Type of wrap if used: semi occlusive with adhesive Gothaplast tape (2.5 cm width) and fixed with Gothaplast tape (5 cm width) around the trunk
- Area of exposure: approximately 10*10 cm

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 h
- Washing (if done): skin was cleaned with mild soap and lukewarm water

SCORING SYSTEM:
See table 7.3.1/1

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 2224

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 2

Irritation parameter:

erythema score

Basis:

animal: 2224

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 3

Irritation parameter:

erythema score

Basis:

animal: 2224

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 4

Irritation parameter:

erythema score

Basis:

animal: 2240

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 5

Irritation parameter:

erythema score

Basis:

animal: 2240

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: undiluted

Results 6

Irritation parameter:

erythema score

Basis:

animal: 2240

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

other: undiluted

Results 7

Irritation parameter:

erythema score

Basis:

animal: 2245

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 8

Irritation parameter:

erythema score

Basis:

animal: 2245

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 9

Irritation parameter:

erythema score

Basis:

animal: 2245

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 10

Irritation parameter:

erythema score

Basis:

animal: 2246

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 11

Irritation parameter:

erythema score

Basis:

animal: 2246

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 12

Irritation parameter:

erythema score

Basis:

animal: 2246

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 13

Irritation parameter:

edema score

Basis:

animal: 2224

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 14

Irritation parameter:

edema score

Basis:

animal: 2224

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 15

Irritation parameter:

edema score

Basis:

animal: 2224

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 16

Irritation parameter:

edema score

Basis:

animal: 2240

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 17

Irritation parameter:

edema score

Basis:

animal: 2240

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 18

Irritation parameter:

edema score

Basis:

animal: 2240

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: day 21

Remarks on result:

other: undiluted

Results 19

Irritation parameter:

edema score

Basis:

animal: 2245

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 20

Irritation parameter:

edema score

Basis:

animal: 2245

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 21

Irritation parameter:

edema score

Basis:

animal: 2245

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 22

Irritation parameter:

edema score

Basis:

animal: 2246

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 23

Irritation parameter:

edema score

Basis:

animal: 2246

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Results 24

Irritation parameter:

edema score

Basis:

animal: 2246

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: day 14

Remarks on result:

other: undiluted

Irritant / corrosive response data:

Application of the test substance HR 02/197007, was associated with a well-defined erythema and a well-defined oedema 24 h after application. The reactions were totally reversible by the 21st day of the test. Skin recovered a normal aspect between the 14th and 21st day of the test.

Any other information on results incl. tables

Table 7.3.1/2: Individual and average scores after 4-hour exposure

Animal No. Weight per kg   Erythema formation observed after hours1 Individual mean values Oedema formation observed after hours2 Individual mean values 1 24 48 72 1 24 48 72 2224 2.9 AL 2 2 2 3 2.33 3 2 2 3 2.33 ML 1 2 2 3 2.33 0 2 2 2 2.00 PL 0 1 0 0 0.33 0 0 0 0 0.00 AR 0 1 0 0 0.33 0 0 0 0 0.00 MR 0 0 0 0 0.00 0 0 0 0 0.00 PR 0 0 0 0 0.00 0 0 0 0 0.00   2240 2.6 AL 2 2 2 3 2.33 3 2 2 3 2.33 ML 1 2 2 3 2.33 1 2 2 2 2.00 PL 0 1 0 0 0.33 0 0 0 0 0.00 AR 0 0 0 0 0.00 0 0 0 0 0.00 MR 0 0 0 0 0.00 0 0 0 0 0.00 PR 0 1 0 0 0.33 0 0 0 0 0.00   2245 2.7 AL 2 2 2 3 2.33 3 2 2 3 2.33 ML 1 2 2 3 2.33 1 2 2 2 2.00 PL 0 1 0 0 0.33 0 0 0 0 0.00 AR 0 1 0 0 0.33 0 0 0 0 0.00 MR 0 0 0 0 0.00 0 0 0 0 0.00 PR 0 0 0 0 0.00 0 0 0 0 0.00   2246 2.9 AL 2 2 2 2 2.00 3 2 2 1 1.67 ML 1 2 2 2 2.00 0 2 2 1 1.67 PL 0 0 0 0 0.00 0 0 0 0 0.00 AR 0 0 0 0 0.00 0 0 0 0 0.00 MR 0 0 0 0 0.00 0 0 0 0 0.00 PR 0 0 0 0 0.00 0 0 0 0 0.00

1: after termination of exposure 2: only the scores from the readings after 24 hours, 48 hours and 72 hours are included in the calculation of the individual values AL: anterior left test filed = 100% ML: middle left test field = 50% PL: posterior left test field = 25% AR: anterior right test field = 10% MR: middle right test field = 1% PR: posterior right test field = 0% (vehicle)

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

HR 02/197007 should be classified as irritating to skin according to the criteria of directive 67/548/EEC and category 2 according to CLP regulation (EC) n°1272/2008.

Executive summary:

A dermal irritation study was conducted according to OECD guideline 404 in compliance with GLP. Four healthy adult New Zealand white rabbits were exposed to 0.5 mL/rabbit of HR 02/197007 on clipped skin of the dorsal area for 4 hours in semi-occlusive conditions. Skin reactions were observed at 1, 24, 48 and 72 h after removal of the substance until day 21.

With undiluted test article, 1 hour after patch removal there was a well-defined erythema and a well-defined oedema in all animals. Mean individual scores for 24, 48 and 72 h observation time points were 2.33, 2.33, 2.33 and 2.00 for erythema and 2.33, 2.33, 2.33 and 1.67 for oedema. The reactions were reversible within 21 days for all animals. The skin recovered a normal aspect between the 14th and the 21st day of the test.

HR 02/197007 should be classified as irritating to skin according to the criteria of directive 67/548/EEC and category 2 according to CLP regulation (EC) n°1272/2008.