Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23-09-2013 To: 31-12-2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met with acceptable devations
Remarks:
To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations ; this may inadvertently enhance scoring observations due to potential abrasion of the skin. The OECD TG 404 guideline specifies pre-exposure clipping only. Additionally, there was some indications that the test item was not fully removed after 4 hours exposure. This would lead to increased potential for classification due to enhancement of response observations.
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:
2014
Report date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Deviation: to facilitate scoring, treated skin areas were re-clipped before the observations. Additionally, some indications that the test item was not fully removed post 4-hour exposure. This would lead to increased potential for classification.
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
see above
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
see above
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000
Deviations:
yes
Remarks:
see above
GLP compliance:
yes (incl. QA statement)
Remarks:
inspected: March 2013 ; signature: May 2013

Test material

Constituent 1
Chemical structure
Reference substance name:
(4R,4aS,8S,8aS)-4-ethyl-8-methyl-decahydronaphthalen-1-one; (4S,4aS,8S,8aR)-4-ethyl-8-methyl-decahydronaphthalen-1-one; (4S,4aS,8S,8aS)-4-ethyl-8-methyl-decahydronaphthalen-1-one
EC Number:
939-400-3
Molecular formula:
C13H22O
IUPAC Name:
(4R,4aS,8S,8aS)-4-ethyl-8-methyl-decahydronaphthalen-1-one; (4S,4aS,8S,8aR)-4-ethyl-8-methyl-decahydronaphthalen-1-one; (4S,4aS,8S,8aS)-4-ethyl-8-methyl-decahydronaphthalen-1-one
Test material form:
liquid
Details on test material:
- Physical state: Liquid
- Storage condition of test material: In refrigerator (2-8°C) in the dark
- Other: clear colourless liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Remarks:
Hsdlf: NZW
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 12 to 24 weeks
- Weight at study initiation: 2574 to 2753 g
- Housing: Individually housed in cages with perforated floors, with shelters and cage enrichment including wooden sticks
- Diet (ad libitum): Global Diet 2030 (Recognised Supplier); provided ad libitum (approximately 100 g per day)
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0
- Humidity (%): 40 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 23-09-2013 To: 31-12-2013

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL.
- Concentration (if solution): Not applicable.

VEHICLE
- Amount applied: Not applicable.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours (initial observation); additional observations are made daily up to Days 7 and 14 to assess the reversibility of skin reactions (as appropriate).
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: Dorsal (2 cm x 3 cm metalline patch secured with adhesive tape)
- % coverage: Not reported
- Type of wrap if used: metalline patch secured with adhesive tape and elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: Four hours after the application, the dressing was removed and the skin cleaned of residual test item using tap water and watery ethanol (50%v/v). Note: that a sticky residue was reported at the 1 hour observation, indicating incomplete removal.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1 hour, 4 hours, 24 hours, 48 hours and 72 hours. Additional observations daily up to 7 or 14 days, as appropriate

SCORING SYSTEM: Draize Scale:
- Method of calculation:
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) *.......................................................................................... 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the
maximum grade for erythema (= 4) is given.
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 millimeter) ........................................................... 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
2.47
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
n = 3
Time point:
24/48/72 h
Score:
3.43
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:
Moderate to severe erythema and moderate or severe oedema in the treated skin areas of the three rabbits, which remained present until termination (after 14 days). Reduced flexibility of the skin was noted for one animal at 72 hours and 7 Days after exposure. Scaliness and/or bald skin were noted for all animals 7 days after exposure, and persisted until termination.
Other effects:
All males showed expected gain in body weight during the study.

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 item is considered to be irritating to the skin.
Executive summary:

The study was performed to OECD TG 404, EU Method B.4, US EPA OPPTS 870.2500 and Japan (JMAFF) 12 Nousan, Notification No 8147 guidelines to assess the primary skin irritancy potential of the test item in accordance with GLP in New Zealand White rabbits. The test item was applied sequentially. Three rabbits were exposed for 4-hour by semi-occluded application of the test item to the intact clipped skin with 0.5 mL test item introduced under a 2 cm x 3 cm semi-occlusive patch. The patch was secured in position with adhesive tape and elasticated bandage. After exposure to the test item the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. Treated sites were reclipped at least 3 hours before observations.Sticky remnants of the test item were present on the skin on Day 1.Moderate to severe erythema and moderate or severe oedema in the treated skin areaswhich remained present until termination (after 14 days). Reduced flexibility of the skin was noted for one animal at 72 hours and 7 Days after exposure. Scaliness and/or bald skin were noted for all males 7 days after exposure, and persisted until termination. Under the conditions of the study, the test item is considered to be a skin irritant.

Applicant assessment indicates: to facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations ; this may inadvertently enhance scoring observations due to potential abrasion of the skin. The OECD TG 404 guideline specifies pre-exposure clipping only. Additionally, there was some indications that the test item was not fully removed after 4 hours exposure. Whilst this may not of invalidated the study conclusions, this would lead to highly conservative conclusion due to increased potential for classification due to enhancement of response observations.