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

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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)

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Name of test material (as cited in study report): HR 02/197007
- Physical state: colourless to slight yellowish liquid
- Lot/batch No.: 000003
- Expiration date of the lot/batch: 31 December 2002
- Storage condition of test material: dark, cold and dry

Species:

rabbit

Strain:

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

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: BI Pharma KG, Biberach, Germany
- Weight at study initiation: 2.6 - 3.3 kg
- Housing: individually in PPO cages
- Diet (e.g. ad libitum): pelleted complete rabbit diet "Altromin 2123" from Altromin, Lage, Germany, ad libitum
- Water (e.g. ad libitum): domestic quality drinking water acidified with hydrochloric acid to pH 2.5, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10 times
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 April 2002 To: 28 April 2002

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

4

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 20 mL 0.9 % sodium chioride solution
- Time after start of exposure: 24 h

SCORING SYSTEM: See table 7.3.3/1

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal: 2186/2.6

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2186/2.6

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2186/2.6

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2102/3.3

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2102/3.3

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2102/3.3

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2106/3.2

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2106/3.2

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2106/3.2

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2107/2.8

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2107/2.8

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 2107/2.8

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

animal: 2186/2.6

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2186/2.6

Time point:

48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2186/2.6

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2102/3.3

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2102/3.3

Time point:

48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2102/3.3

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2106/3.2

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2106/3.2

Time point:

48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2106/3.2

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2107/2.8

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2107/2.8

Time point:

48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal: 2107/2.8

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: 2186/2.6

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2186/2.6

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2186/2.6

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2102/3.3

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2102/3.3

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2102/3.3

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2106/3.2

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2106/3.2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2106/3.2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2107/2.8

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2107/2.8

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal: 2107/2.8

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal: 2186/2.6

Time point:

24 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2186/2.6

Time point:

48 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2186/2.6

Time point:

72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2102/3.3

Time point:

24 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2102/3.3

Time point:

48 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2102/3.3

Time point:

72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2106/3.2

Time point:

24 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2106/3.2

Time point:

48 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2106/3.2

Time point:

72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2107/2.8

Time point:

24 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2107/2.8

Time point:

48 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 2107/2.8

Time point:

72 h

Score:

0

Max. score:

2

Irritant / corrosive response data:

See Table 7.3.2/2

Table 7.3.2/2: detailed results

Animal n°/weight (kg)	Ocular lesions	Score at timepoint				Individual mean score
		1 h	24 h	48 h	72 h
2186/2.6	Cornea opacity	0	0	0	0	0
	Iris	0	0	0	0	0
	Conjunctiva	1	1	1	0	0.67
	Chemosis	2	1	0	0	0.33
2102/3.3	Cornea opacity	0	0	0	0	0
	Iris	0	0	0	0	0
	Conjunctiva	1	1	1	0	0.67
	Chemosis	1	1	0	0	0.33
2106/3.2	Cornea opacity	0	0	0	0	0
	Iris	0	0	0	0	0
	Conjunctiva	1	1	1	0	0.67
	Chemosis	1	1	0	0	0.33
2107/2.8	Cornea opacity	0	0	0	0	0
	Iris	0	0	0	0	0
	Conjunctiva	1	1	1	0	0.67
	Chemosis	1	1	0	0	0.33

Interpretation of results:

GHS criteria not met

Conclusions:

Under test conditions, HR 02/197007 is not irritating to eyes and should not be classified for eye irritation according to the criteria of directive n°67/548/EEC and CLP regulation (EC) n°1272/2008.

Executive summary:

In an eye irritation study conducted according to the OECD Guideline 405 and in compliance with GLP, 4 healthy adults female albino rabbits were exposed to 0.1 mL of undiluted HR02/197007 in one eye while the other eye corresponded to the control. The eyes were examined and scored unwashed after 1 h and 24 h and then washed with 20 mL 0.9% sodium chloride solution. Changes were observed at 48 and 72 hours after dosing and graded.

The individual mean score for all animals were 0 for cornea opacity, 0 for iris lesion, 0.67 for conjunctiva and 0.3 for chemosis. All effects were reversible within 72 h.

Under these test conditions, HR 02/197007 isconsidered as not irritating to eyes and should not be classified according to the criteria of directive 67/548/EEC and CLP regulation (EC) n°1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available