1,6,10-Dodecatriene, 7,11-dimethyl-3-methylene-, (6E)-, hydrogenated

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 JUne 2014 to 22 July 2014

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 affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1.25H Farnesene

IUPAC Name:

1.25H Farnesene

Test material form:

other: liquid

Details on test material:

Identification: 1.25H Farnesene
Batch: RV-752-153-2
Purity: 98.92%
Physical state / Appearance: clear, colorless liquid
Expiry date: 01 March 2015
Storage Conditions: room temperature in the dark

A Certificate of Analysis supplied by the Sponsor is given in Appendix 1 (attachment 1)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.51 to 2.85 kg and were twelve to twenty weeks old. After an acclimatization 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 cages. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) 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. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled 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 affected the purpose or integrity of the study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL of the test item was applied directly to the skin

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

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 animals with a healthy intact epidermis by gross observation were selected for the study.

One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.

One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.

After consideration of the skin reactions produced in the first animal, an additional two animals were treated with 0.5 mL of test item. 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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: Erythema/Eschar Formation

Basis:

animal: 74424 male

Time point:

other: Highest score at 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 2

Irritation parameter:

other: Erythema/Eschar Formation

Basis:

animal: 74483 Male

Time point:

other: Highest score at 24, 48, 72 hours and 7, 14 days

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Positive criterion according to the Globally Harmonized System of Classification and Labelling of Chemicals at 24, 48 and 72 hours. Moderate desquamation observed at 7 days.

Results 3

Irritation parameter:

other: Erythema/Eschar Formation

Basis:

animal: 74484 male

Time point:

other: Highest score at 24, 48, 72 hours and 7, 14 days

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Positive criterion according to the Globally Harmonized System of Classification and Labelling of Chemicals at 24, 48 and 72 hours. Moderate desquamation observed at 7 days.

Results 4

Irritation parameter:

other: Oedema Formation

Basis:

animal: 74424 male

Time point:

other: Highest score at 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No evidence of skin irritation

Results 5

Irritation parameter:

other: Oedema Formation

Basis:

animal: 74483 male

Time point:

other: Highest score at 24, 48, 72 hours and 7, 14 days

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Positive criterion according to the Globally Harmonized System of Classification and Labelling of Chemicals at 24, 48 and 72 hours.

Results 6

Irritation parameter:

other: Oedema Formation

Basis:

animal: 74484 male

Time point:

other: Highest score at 24, 48, 72 hours and 7, 14 days

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Positive criterion according to the Globally Harmonized System of Classification and Labelling of Chemicals at 24, 48 and 72 hours.

Irritant / corrosive response data:

Skin Reactions
3-Minute Exposure Period
The individual scores for erythema/eschar and edema are given in Table 1.

No evidence of skin irritation was noted during the study.


1-Hour Exposure Period
The individual scores for erythema/eschar and edema are given in Table 1.

No evidence of skin irritation was noted during the study.


4-Hour Exposure Period
The individual scores for erythema/eschar and edema are given in Table 2.

No evidence of skin irritation was noted at the test site of the initial treated animal during the study.

Well defined erythema and slight edema were noted at the test sites of the second and third treated animals immediately and 1 hour after patch removal and at the 24, 48 and 72 Hour observations. Moderate desquamation was noted at these two treated skin sites at the 7 Day observation.

Other effects:

Body Weight
Individual body weights and body weight change are given in Table 3.

All animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Table1     Individual Skin ReactionsFollowing 3-Minute and 1-Hour Exposures

Skin Reaction	Observation Time (following patch removal)	Individual Scores
		Rabbit Number and Sex 74424Male
		3-Minute Exposure	1-Hour Exposure
Erythema/Eschar Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	0
	48 Hours	0	0
	72 Hours	0	0
Edema Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	0
	48 Hours	0	0
	72 Hours	0	0

Table 2     Individual Skin Reactions Following 4-Hour Exposure

Skin Reaction	Observation Time (following patch removal)	Individual Scores
		Rabbit Number and Sex
		74424Male	74483Female	74484Female
Erythema/Eschar Formation	Immediately	0	2	2
	1 Hour	0	2	2
	24 Hours	0	2+	2+
	48 Hours	0	2+	2+
	72 Hours	0	2+	2+
	7 Days	-	0D	0D
	14 Days	-	0	0
Edema Formation	Immediately	0	2	2
	1 Hour	0	2	2
	24 Hours	0	2+	2+
	48 Hours	0	2+	2+
	72 Hours	0	2+	2+
	7 Days	-	0	0
	14 Days	-	0	0

D=   Moderate desquamation

- =    Not applicable

+ =   Positive criterion according to theGlobally Harmonized System of Classification and Labelling of Chemicals

Table 3     Individual Body Weights and Body Weight Change

Rabbit Number and Sex	Individual Body Weight (kg)		Body Weight Change (kg)
74424 Male	Day 0	Day 3	0.07
	2.85	2.92
74483 Female	Day 0	Day 14	0.21
	2.73	2.94
74484 Female	Day 0	Day 14	0.25
	2.51	2.76

Interpretation of Results

Interpretation According to Regulation (EC) No 1272/2008, Relating to the Classification, Labelling and Packaging of Substances and Mixtures

Skin Corrosive Category and Subcategories
	Corrosive Subcategory			Corrosive in >= 1 of 3 animals
				Exposure		Observation
Category 1: Corrosive	1A			<= 3 minutes		<= 1 hour
	1B			>3 minutes - <= 1 hour		<= 14 days
	1C			>3 minutes - <= 4 hours		<= 14 days
Skin Irritation Category
Category		Criteria
Category 2: Irritant		(1)	Mean value of >= 2,3 - >= 4,0 for erythema/eschar of for edema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or
		(2)	Inflammation that persist to the end of the observation period normally 14 days in a least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or
		(3)	in some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less that the criteria above.
Label Elements for Skin Corrosion/Irritation
Classification		Category 1A / 1B / 1C			Category 2
GHS Pictograms
Signal word		Danger			Warning
Hazard Statement		H314: Causes severe skin burns and eye damage			H315: Causes skin irritation
Precautionary Statement Prevention		P260 P264 P280			P264 P280
Precautionary Statement Response		P301 + P330 + P331 P303 + P361 + P353 P363 P304 + P340 P310 P321 P305 + P351 + P338			P302 + P352 P321 P332 + P313 P362
Precautionary Statement Storage		P405
Precautionary Statement Disposal		P501

Interpretation According to the Globally Harmonized System of Classification and Labelling of Chemicals

Skin Corrosive Category and Subcategories
Category 1: Corrosive	Corrosive subcategory			Corrosive in >= 1 of 3 animals
				Exposure	Observation
Corrosive	1A			<=3 minutes	<= 1 hour
	1B			> 3 minutes - <= 1 hour	<= 14 days
	1C			> 3 minutes - <= 4 hours	<= 14 days
Skin Irritation Category
Categories		Criteria
Irritant (Category 2)		(1)	Mean value of >= 2, 3 - <= 4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or
		(2)	Inflammation that persist to the end of the observation period normally 14 days in a least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or
		(3)	in some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less that the criteria above.
Mild Irritant (Category 3)			Mean value of >= 1.5 - <= 2.3 for erythema/eschar or for oedema from gradings in at least 2 of 3 tested animals from grades at 24, 48 and 72 hours or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions (when not included in the current category above).

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Remarks:

Migrated information

Conclusions:

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

The test item was also classified as Category 3 (Mild irritant) according to the Globally Harmonized System of Classification and Labelling of Chemicals.

Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item following single, 3‑Minute, 1 and 4‑Hour, semi‑occluded applications to the intact rabbit skin.

 

Results

3‑Minute and 1‑Hour semi-occluded applications of the test item to the intact skin of one rabbit produced no evidence of skin irritation.

A single 4‑Hour, semi occluded application of the test item to the intact skin of three rabbits produced well‑defined erythema, slight edema and moderate desquamation at two treated skin sites. No evidence of skin irritation was noted at one treated skin site. No corrosive effects were noted.

 

Conclusion

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

 

The test item was also classified as Category 3 (Mild irritant) according to the Globally Harmonized System of Classification and Labelling of Chemicals.