1-Decene, 1-ethoxy-

Endpoint summary

Description of key information

Skin irritation: Irritating (OECD TG 404)
Eye irritation: Not irritating (OECD TG 405)   

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:

Between 02 October 2001 and 16 October 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols and under GLP conditions.

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

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: A reputable UK supplier
- Age at study initiation: Twelve to sixteen weeks old
- Weight at study initiation: 2.0 to 3 .5 kg
- Housing: Individually housed in suspended metal cages.
- Diet: Free access to food (Certified Rabbit Diet (Code 5322) supplied by a reputable UK supplier
- Water: Free access to mains drinking water
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 to 23°C
- Humidity: 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod: Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.









.

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml of the test material

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animalswith a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returnedto their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cottonwool soaked in 74% Industrial Methylated Spirits.

Irritation parameter:

erythema score

Basis:

animal: #37

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

other: Moderate desquamation and reduced regrowth of fur observed at 14 d

Irritation parameter:

erythema score

Basis:

animal: #43

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: Crust formation and reduced regrowth of fur observed at 14 d

Irritation parameter:

erythema score

Basis:

animal: #49

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Remarks on result:

other: Moderate desquamation and reduced regrowth of fur observed at 14 d

Irritation parameter:

edema score

Basis:

animal: #37

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

edema score

Basis:

animal: #43

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritation parameter:

edema score

Basis:

animal: #49

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 d

Irritant / corrosive response data:

Well-defined erythema was noted at all treated skin sites one hour after patch removal and persisted at all treated skin sites at the 24. 48 and 72-hour observations. Other reactions noted were light brown discolouration of the epidermis, skin reactions extending approximately 4 cm beyond the site of application. loss of skin elasticity, crust formation. moderate desquamation and reduced re growth of fur. Adverse reactions prevented the evaluation of erythema at the 7 -day observation.
Very slight to slight oedema was noted at all treated skin sites one hour after patch removal with slight oedema noted at all treated skin sites at the 24, 48 and 72-hour observations. Adverse reactions prevented evaluation of oedema at the 7-day observation.

Individual Skin Reactions

Skin Reaction	Observation Time	Individual Scores – Rabbit Number and Sex			Total
		37 Female	43 Male	49 Male
ErythemalEschar Formation	1 Hour	2	2	2	(6)
	24 hours	2 R	2 Br	2 R	6
	48 Hours	2 RLe	2 BrLe	2 RLe	(6)
	72 Hours	2 RLe	2 BrLe	2 RLe	6
	7 Days	?eCf	?eCf	?eCf	(0-12)
	14 Days	0 DFr	0 CfFr	0 DFr	(0)
Oedema Formation	1 Hour	1	2	2	(5)
	24 hours	2	2	2	6
	48 Hours	2	2	2	(6)
	72 Hours	2	2	2	6
	7 Days	?od	?od	?od	(0-12)
	14 Days	0	0	0	(0)
Sum of 24 and 72-hour Readings (S):		24
Primary Irritation Index (S/6):		24/6 = 4.0
Classification:		MODERATE IRRITANT

( ) = Total values not used for calculation of primary irritation index

Br = Light brown discolouration of the epidermis

Cf= Crust formation

D = Moderate desquamation

Fr = Reduced regrowth of fur

Le = Loss of skin elasticity

R = Reaction extends beyond site of application

?e = Adverse reactions prevent evaluation of erythema

?od = Adverse reactions prevent evaluation of oedema

Interpretation of Results

Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize Scheme

The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the,,, p.47:

Primary Irritation Index	Classification of Irritancy
0	Non-irritant
> 0 to 2	Mild irritant
> 2 to 5	Moderate irritant
> 5 to 8	Severe irritant

If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test material is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.

Interpretation of results:

moderately irritating

Remarks:

Migrated information Category 2: Irritant Criteria used for interpretation of results: EU

Conclusions:

The test material produced a primary irritation index of 4. 0 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Executive summary:

The irritant effects of Arctical to rabbit skin was assessed in a GLP study according to OECD Guideline No. 404. A quantity of 0.5 ml of test substance was applied to the intact skin of three rabbits. Four hours after application the corset and patches were removed from each animal. Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of irritation and scored. Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions. In accordance with the classification criteria set out in CLP Regulation (EC) 1272/2008 the test material is considered to be Category 2: Irritant

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:

Between 11 October 2001 and 19 October 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols and under GLP conditions.

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)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three New Zealand White rabbits were supplied by a reputable supplier.

At the start of the study the animals were in the weight range of 2.0 to 3.5 kg and were twelve to sixteen weeks old.

After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food ( from a reputable supplier. For full details please see full study report) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting wascontrolled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affectedthe purpose or integrity of the study.

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and was used for control purposes.

Amount / concentration applied:

0.1 ml of the test material

Duration of treatment / exposure:

Up to 1 hour

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 animals were tested in total. (After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. )

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.
Initially, a single rabbit was treated. A volume of 0.1 ml of the test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.
The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale.
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).
Any other ocular effects were also noted.

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal: #148

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal: #57

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal: #140

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: #148

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: #57

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: #140

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #148

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #57

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #140

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal: #148

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal: #57

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal: #140

Time point:

other: Mean of scores at 24, 48 and 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.

Minimal conjunctival irritation was noted in all treated eyes one hour after treatment. All treated eyes appeared normal at the 24-hour observation.

Interpretation of Results

The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of cornea involved). For each tissue the score was calculated as follows:

Score for conjunctivae =         (A + B + C) x 2
Score for iris                  =         D x 5
Score for cornea           =         (E x F) x 5

Using the numerical data obtained a modified version of the system described by Kay J H and Calandra J C, J. Soc. Cosmet. Chem., 1962 13 281-289 was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material.

If evidence of irreversible ocular damage is noted, the test material will be classified as corrosive to the eye.

Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	148 Male				57 Male				140 Male
	IPR= 3				IPR = 1+				IPR = 0+
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
CORNEA
E = Degree of Opacity	0	0	0	0	0	0	0	0	0	0	0	0
F = Area of Cornea Involved	0	0	0	0	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0
IRIS
D	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	1	0	0	0	1	0	0	0	1	0	0	0
B = Chemosis	1	0	0	0	1	0	0	0	1	0	0	0
C = Discharge	1	0	0	0	0	0	0	0	0	0	0	0
Score (A + B + C) x 2	6	0	0	0	2	0	0	0	2	0	0	0
Total Score	6	0	0	0	2	0	0	0	2	0	0	0

IPR= Initial pain reaction

Individual Total Scores and Group Mean Scores for Ocular Irritation

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours
148Male	6	0	0	0
57 Male	2	0	0	0
140 Male	2	0	0	0
Group Total	10	0	0	0
Group Mean Score	3.3	0.0	0.0	0.0

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the classification criteria set out in CLP Regulation (EC) 1272/2008 the test substance is not considered to be irritating to eyes.

Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit in a GLP study according to OECD Guideline 405. Initially, a single rabbit was treated. A volume of 0.1 ml of the test material was placed into the conjunctival sac of the right eye. The left eye remained untreated and was used for control purposes. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours according to the method of Draize. A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal at the 24 -hour observation. According to the classification criteria set out in CLP Regulation (EC) 1272/2008 the test substance is not considered to be irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation:

The irritant effects of Arctical to rabbit skin was assessed in a GLP study according to OECD Guideline No. 404. A quantity of 0.5 ml of test substance was applied to the intact skin of three rabbits. Four hours after application the corset and patches were removed from each animal. Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of irritation and scored. Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions. On day 14, the erythema score was 0, still some skin reactions were noted (e.g. desquamation) that are considered severe enough to warrant classification as skin irritant 2 (H315), in accordance with the classification criteria set out in CLP Regulation (EC) 1272/2008).

Eye irritation

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit in a GLP study according to OECD Guideline 405. Initially, a single rabbit was treated. A volume of 0.1 ml of the test material was placed into the conjunctival sac of the right eye. The left eye remained untreated and was used for control purposes.After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours according to the method of Draize. A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal at the 24 -hour observation. According to the classification criteria set out in CLP Regulation (EC) 1272/2008 the test substance is not considered to be irritating to eyes.

Justification for selection of skin irritation / corrosion endpoint:
The result of the study is reliable and adequate for covering the endpoint

Justification for selection of eye irritation endpoint:
The result of the study is reliable and adequate for covering the endpoint.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Based on the results of the studies, Arctical needs to be classified for skin irritation but not for eye irritation resulting in irritating to skin, category 2 (H315), in accordance with Regulation (EC) No. 1272/2008 or R38 in accordance with Directive 67/548/EEC.