Dodecene, hydroformylation products, low-boiling

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion, other

Remarks:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

between 23 July 2008 and 26 August 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affcet the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of Inspection - 21/08/07 Date of Signature - 15/10/07

Test material

Test material information

Constituent 1

Reference substance name:

Dodecene, hydroformylation products, low-boiling

EC Number:

271-240-3

EC Name:

Dodecene, hydroformylation products, low-boiling

Cas Number:

68526-92-1

Molecular formula:

The substance consists of 46 isomers of unsaturated and branched dodecene structures (see Test Report No. A170002983).

IUPAC Name:

Dodecene, hydroformylation products, low-boiling

Details on test material:

- Sponsor's identification: Oxooil LS 13 (CAS No. 68526-92-1)
- Description: Clear colourless liquid
- Date received: 14 July 2008
- Storage conditions : room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: day 1 To: day 14

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped free from fur using veterinary clippers

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml
- Concentration (if solution): Undiluted as supplied


VEHICLE:
Not applicable

Duration of treatment / exposure:

One patch was applied to the back of each rabbit, and was allowed to remain in contact with the skin for a period of four hours.

Observation period:

Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation.

Number of animals:

One rabbit was initially treated. After consideration of the skin reactions produced in the first animal, two additional animals were treated.

Details on study design:

TEST SITE
- Area of exposure: 3 areas each 2.5 cm x 2.5 cm
- % coverage: Not recorded
- Type of wrap if used: surgical adhesive tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not applicable
- Time after start of exposure: One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application.


SCORING SYSTEM:
Standard EU Classification and Labelling Scoring system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: Mean 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Light brown discolouration of the epidermis, Loss of skin elasticity and Loss of skin flexibility at 48, 72 hours and 7 days

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: Mean 24, 48 and 72 hours

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

3-Minute Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 1.
Well-defined erythema and very slight oedema were noted at the treated skin site at the 24 and 48‑hour observations with very slight erythema and very slight oedema at the 72‑hour observation. Other skin reactions noted at the treated skin site at the 48-hour observation were loss of skin elasticity and light brown discolouration of the epidermis with loss of skin elasticity and crust formation noted at the 72‑hour observation. Slight desquamation was noted at the treated skin site at the 7-day observation. 
The treated skin site appeared normal at the 14-day observation.

1-Hour Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 1.
Very slight erythema was noted at the treated skin site one hour after patch removal with well‑defined erythema and very slight oedema noted at the 24, 48 and 72-hour observations. Other skin reactions noted at the treated skin site at the 48 and 72-hour observations were loss of skin flexibility and/or elasticity and light brown discolouration of the epidermis. Moderate desquamation was noted at the treated skin site at the 7-day observation.
The treated skin site appeared normal at the 14-day observation.

 4-Hour Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 2.
Very slight erythema was noted at all the treated skin sites one hour after patch removal with well defined erythema and very slight to slight oedema at the 24, 48 and 72-hour observations. Very slight erythema was noted at all treated skin sites at the 7‑day observation. Light brown discolouration of the epidermis and loss of skin flexibility and elasticity were noted at all treated
skin sites at the 48 and 72‑hour observations. Crust formation was noted at all treated skin sites at the 7‑day observation. 
All treated skin sites appeared normal at the 14-day observation.

Any other information on results incl. tables

Bodyweight:

Individual bodyweights and bodyweight changes are given in Table 3.

All animals showed expected gain in bodyweight during the study.

Table1               Individual Skin Reactions Following 3-Minute and 1-Hour Exposures

Skin Reaction	Observation Time	Individual Scores - Rabbit Number and Sex
		67625Male
		3-Minute Exposure	1-Hour Exposure
Erythema/Eschar Formation	1 Hour	0	1
	24 Hours	2	2
	48 Hours	2LeBr	2LeBr
	72 Hours	1LeCf	2LeLfBr
	7 Days	0D	0D*
	14 Days	0	0
Oedema Formation	1 Hour	0	0
	24 Hours	1	1
	48 Hours	1	1
	72 Hours	1	1
	7 Days	0	0
	14 Days	0	0

 

D= Slight desquamation

D* = Moderate desquamation

Br = Light brown discolouration of the epidermis

Le = Loss of skin elasticity

Lf = Loss of skin flexibility

Cf = Crust formation

Table2               IndividualSkin ReactionsFollowing 4-Hour Exposure

Skin Reaction	Observation Time	Individual Scores – Rabbit Number and Sex			Total
		67625Male	67676Male	67678Male
Erythema/Eschar Formation	1 Hour	1	1	1	(3 )
	24 Hours	2	2	2	6
	48 Hours	2BrLeLf	2BrLeLf	2BrLeLf	( 6 )
	72 Hours	2BrLeLf	2BrLeLf	2BrLeLf	6
	7 Days	1Cf	1Cf	1Cf	( 3 )
	14 Days	0	0	0	( 0 )
Oedema Formation	1 Hour	0	0	0	( 0 )
	24 Hours	1	1	1	3
	48 Hours	2	2	2	( 6 )
	72 Hours	2	2	2	6
	7 Days	0	0	0	( 0 )
	14 Days	0	0	0	( 0 )
Sum of 24 and 72-hour Readings (S):              21
Primary Irritation Index (S/6)                             :              21/6 = 3.5
Classification                                                       :              MODERATE IRRITANT

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

Cf = Crust formation

Br = Light brown discolouration of the epidermis

Le = Loss of skin elasticity

Lf = Loss of skin flexibility

Table3               Individual Bodyweights and Bodyweight Change

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 14
67625Male	2.97	3.12	0.15
67676Male	2.71	3.04	0.33
67678Male	2.50	2.87	0.37

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information (but not classifed according to EC Regulation No. 1272/2008) Criteria used for interpretation of results: EU

Conclusions:

In a skin irritation test conducted according to OECD guideline 404 and GLP principles, no corrosive or irreversible effects were noted. The average erythema and oedema score at 24, 48 and 72 hours after exposure was 2 and 1.66 resp, therefore this substance is not classified for skin irritation according to EC Regulation No. 1272/2008. In accordance with EC Directive No. 67/548, the substance should be classified with Xi; R38.
Based on the results obtained in this study, the substance should be labelled with EUH066 – “Repeated exposure may cause skin dryness or cracking”

Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted)

§        Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 2004/73/EC

Results. 3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and slight oedema. Other skin reactions noted were light brown discolouration of the epidermis, loss of skin elasticity and flexibility and crust formation. All treated skin sites appeared normal at the 14-day observation. No corrosive effects were noted.

Conclusion: 

No corrosive effects were noted. The average erythema and oedema score at 24, 48 and 72 hours after exposure was 2 and 1.66 resp, therefore this substance is not classified for skin irritation according to EC Regulation No. 1272/2008. In accordance with EC Directive No. 67/548, the substance should be classified with Xi; R38. Based on the results obtained in this study, the substance should be labelled with EUH066 – “Repeated exposure may cause skin dryness or cracking”