Registration Dossier

Administrative data

Description of key information

In an OECD guideline 404 study conducted in compliance with GLP, the test substance was not irritating to the skin. 
Due to the high volatility of the substance an eye irritation study is technically not feasible to conduct. However, in repeated dose inhalation toxicity studies, including those conducted using whole body exposure no signs of skin, eye and respiratory irritation were observed.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with GLP and OECD guideline, available as unpublished report, no restrictions, fully adequate for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Inc, Denver PA USA
- Weight at study initiation: 2.7 - 3.4 kg
- Housing: individually in suspended cages; absorbant paper beneath cages was changed at least 3 times a week
- Diet: ad libitum, PMI Rabbit Chow (Diet #5321)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled and monintored but specific details not provided in report
- Humidity (%): controlled and monitored but specific details not included in report
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours/12hours
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
4 hours
Observation period:
up to 72 hours following patch removal
Number of animals:
3 (1 male, 2 females)
Details on study design:
Approx. 24 hours prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. Each dose sit was approx. 6 cm2. The test article was dosed by volume, 0.5 mL/site and placed over a 2x3 cm gauze patch. Gentle pressure was applied to aid in the distribution of the test article over the prepared site. The patch was secured with non-irritating tape. The torsi was covered with a piece of porous dressing (semi-occlusive) large enough to cover the dose site with at least 5 cm square to spare on all sides of the gauze patch. Porous, non-irritating tape was used to encircle the trunk of the animal. The test substance was kept in contact with the skin for 4 hours at which the wrappings and patches were removed. Residual test article was removed from the test site by gently washing with distilled water at the end of the exposure period, prior to scoring for dermal reactions.
The test sites were scored for dermal irritation at 1, 24, 48, 72 hours following patch removal. Erythema and edema were scored according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction.
Body weights were recorded pretest and at termination. Animals were observed for mortality, toxicological and pharmacological effects at each dermal observation period.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Average 24, 48, and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Average 24, 48, and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No irritation or corrosion observed in any of the 3 rabbits at any time point
Other effects:
No abnormal physical signs were observed. All three animals experienced body weight gain.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an OECD guideline 404 study conducted in compliance with GLP, the test substance was not irritating to the skin.
Executive summary:

In a skin irritation study performed in accordance with GLP and OECD guideline 404 three New Zealand White rabbits were exposed semi-occlusive to the test substance. After 4 hours of exposure the test article was removed and the skin was examined 1, 24, 48 and 72 hours after termination of exposure. No erythema or edema was noted at any observation period. No abnormal physical signs were observed. All three animals experienced body weight gain. The test substance was found not to be skin irritant when applied topically to the rabbit.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

In a skin irritation study performed in accordance with GLP and OECD guideline 404 three New Zealand White rabbits were exposed semi-occlusive to the test substance (MB Research laboratories, 2012). After 4 hours of exposure the test article was removed and the skin was examined 1, 24, 48 and 72 hours after termination of exposure. No erythema or edema was noted at any observation period. No abnormal physical signs were observed. All three animals experienced body weight gain. The test substance was found not to be skin irritant when applied topically to the rabbit.


Justification for selection of skin irritation / corrosion endpoint:
One GLP-compliant OECD guideline 404 skin irritation study is available. This study is sufficiently adequate for this endpoint.

Justification for classification or non-classification

Based on a skin irritation study in rabbits and based on repeated dose inhalation toxicity studies, including those conducted using whole body exposure no signs of skin, eye, and respiratory irritation were observed. It can therefore be concluded that the substance does not need to be classified for skin, eye, and respiratory irritation according to EU Directive 67/548/EEC (DSD) and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulations (EC) No. 1272/2008.