5,9-dimethyldec-4-enal

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01-03-2016 to 15-03-2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

Justification for type of information:

Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

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)

Remarks:

inspected: June 2015; signature: September 2015

Test material

Test material information

Constituent 1

Reference substance name:

(4E)-5,9-dimethyldec-4-enal; (4Z)-5,9-dimethyldec-4-enal

EC Number:

943-495-7

Cas Number:

689-65-6

Molecular formula:

C12H22O

IUPAC Name:

(4E)-5,9-dimethyldec-4-enal; (4Z)-5,9-dimethyldec-4-enal

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: Approximately 4 °C, in the dark
- Other: clear colourless

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: recognised animal supplier
- Age at study initiation: 12 - 52 weeks
- Weight at study initiation: 2.93 or 3.24 kg
- Housing: Individually housed in suspended cages.
- Diet: certified rabbit diet ad libitum
- Water: mains drinking water ad libitum
- Acclimation period: at least 5 days

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

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): Test material was used as supplied.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours (initial observation); additional observations are made on Days 7 and 14 to assess the reversibility of skin reactions (as appropriate).

Number of animals:

2; following the guideline sequential testing approach

Details on study design:

TEST SITE
- Area of exposure: dorsal
- Type of wrap if used: semi-occlusive (2.5 cm x 2.5 cm cotton gauze patch secured with surgical adhesive tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema and Eschar Formation
No erythema _________________________________________________________________________0
Very slight erythema (barely perceptible) ________________________________________________1
Well-defined erythema ________________________________________________________________2
Moderate to severe erythema __________________________________________________________3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) ________________4

Oedema Formation
No oedema __________________________________________________________________________0
Very slight oedema (barely perceptible) _________________________________________________1
Slight oedema (edges of area well-defined by definite raising) _____________________________2
Moderate oedema (raised approximately 1 millimetre) ____________________________________3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) ___4
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean score (n=2); Glossy skin, slight desquamation and reduced regrowth of fur was seen at day 14

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean score (n=2); see comments above

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean score (n=2); see comments above

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean score (n=2); see comments above

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean score (n=2); Glossy skin, slight desquamation and reduced regrowth of fur was seen at day 14

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean score (n=2); see comments above

Results 7

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean score (n=2); see comments above

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: mean score (n=2); see comments above

Irritant / corrosive response data:

- Erythema: Well defined erythema (score = 2) and slight edema (score = 2) at treated skin sites were noted immediately, at 1 hour and at 24, 48 and 72 hours after patch removal. The erythema extended approximately 10 mm beyond the test site 1 hour after patch removal and at the 24, 48, 72 Hour and 7 Day observations.
- Edema: and slight edema (score = 2) was noted immediately, at 1 hour and at 24, 48 and 72 hours after patch removal.
- Reversibility of effects:
1. Day 7: Inflammation (erthymea and edema) persisted (score = 2) with light brown discoloration of the epidermis and loss of skin elasticity and flexibility were noted at both treated sites.
2. Day 14: Inflammation (erthymea and edema) had fully reversed (score = 0) in all treated sites; however, glossy skin, slight desquamation and reduced regrowth of fur were noted at both treated skin sites at the 14 Day observation.

Other effects:

Light brown discoloration of the epidermis and loss of skin elasticity and flexibility were noted at both treated skin sites at the 7 Day observation. Glossy skin, slight desquamation and reduced regrowth of fur were noted at both treated skin sites at the 14 Day observation.
Both organisms showed expected body weight gain during the course of the study. There was no clinical signs of toxicity reported during the duration of the test.

Any other information on results incl. tables

Table 1. Individual skin reactions

Skin Reaction	Observation Time (following patch removal)	Individual Scores
		Number and Sex
		#1 (Female)	#2 (Female)
Erythema/Eschar Formation	Immediately	2	2
	1 Hour	2R	2R
	24 Hours	2R	2R
	48 Hours	2R	2R
	72 Hours	2R	2R
	7 Days	2RBrLeLf	2RBrLeLf
	14 Days	0GDFr	0GDFr
Edema Formation	Immediately	2	2
	1 Hour	2	2
	24 Hours	2	2
	48 Hours	2	2
	72 Hours	2	2
	7 Days	2	2
	14 Days	0	0

R = Reaction extended approximately 10 mm beyond the test site

Br = Light brown discoloration of the epidermis

Le = Loss of skin elasticity

Lf = Loss of skin flexibility

G = Glossy skin

D = Slight desquamation

Fr = Reduced regrowth of fur

 

Mean scores per organism at 24, 48 and 72h:

Erythemea/Escar Formation:

1: total = 2.0 ; mean score = 2.0

2: total = 2.0; mean score = 2.0

Edema Formation:

1: total = 2.0; mean score = 2.0

2. total = 2.0; mean score = 2.0

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the test material is considered to be irritating.

Executive summary:

The study was performed to OECD TG 404, EU Method B.4 and the Japanese MAFF (2000) and US EPA OPPTS 870.2500 to assess the primary skin irritancy potential of the test substance in accordance with GLP in New Zealand White rabbits. Following single 4-Hour, semi-occluded applications to the intact rabbit skin. 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 clipped skin to assess the irritancy potential of the test item. The patch was secured in position with a strip of surgical adhesive tape. After 4 hours of exposure to the test substance, the patches were removed and individual dose sites were scored at approximately 1, 24, 48, 72 hours and 7 and 14 days, respectively. A single 4-Hour, semi occluded application of the test item to the intact skin of two rabbits produced well-defined erythema and slight edema at both skin sites at 1 hour, 24 through 72 hours after patch removal. No corrosive effects were noted. Other skin reactions noted were light brown discoloration of the epidermis, loss of skin elasticity and flexibility, glossy skin, slight desquamation and reduced regrowth of fur. Mean scores for following grading at 24, 48 and 72h were 2.0 in erythema and eschar and 2.0 in edema scoring criteria. At day 14, mean scores were zero for erythema and edema, respectively. Glossy skin, slight desquamation and reduced fur growth persisted. Under the conditions of the study, the substance is considered to be a skin irritant.