Registration Dossier

Administrative data

Description of key information

In vivo skin irritation testing was performed that did not show the test substance to be corrosive to the skin. An in vitro skin irritation study was performed in accordance with the OECD Testing Guideline 439 on the registered substance and concluded that it meets the criteria for classification as irritant to the skin.

An in vitro eye irritation study was performed in accordance with the OECD Testing Guideline 437 on the registered substance and concluded it does not meet the criteria for classification as damaging or irritant to the eye.

In vivo testing was performed before the implementation of REACH for the purpose of other regulations and therefore is not in breach of the Animal Welfare Legislation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
Principles of method if other than guideline:
EPISKIN Skin Irritation Test-42 Hours
GLP compliance:
yes
Species:
human
Strain:
other: Three dimensional human skin model
Details on test animals and environmental conditions:
The test involves the application of the test substance for 15 minutes to the EPISKIN threedimensional human skin model. The model consists of normal, human-derived epidermal keratinocytes which have been seeded on a dermal substitute consisting of a collagen type 1 matrix coated with type IV collagen. After 13 days in culture a multilayered, highly differentiated model of the human epidermis with a functional multi-layered stratum corneum has formed. The epidermis surface area supplied is 0.38 cm^2. The EPISKIN kits include assay medium, maintenance medium, 12 well plates and the tissues which are shipped on nutritive agar.
Type of coverage:
other: In vitro
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
The test substance, positive and negative controls were in liquid form and were applied by dispensing a volume of 10 µl over each tissue using a positive displacement pipette.
Duration of treatment / exposure:
Exposure over 15 minutes.
Number of animals:
N/A
Irritation / corrosion parameter:
% tissue viability
Value:
14.3
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
Basis: mean. Remarks: +/- 2.7 %
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In vitro skin irritation using the EPISKIN method gave a moderately irritating response.
Executive summary:

The skin irritation potential of the test substance was determined in vitro using the EPISKIN human epidermis model. The test substance was applied to EPISKIN human epidermis skin constructs. The constructs consisted of normal, human-derived epidermal keratinocytes, which had been cultured to form a multilayered, highly differentiated model of the human epidermis with a functional multilayered stratum corneum. The cell viability of the multi layers was determined by mitochondrial dehydrogenase activity. The prediction model uses the percentage viability values (compared to negative control viability) to identify irritant and non-irritant substances. The test substance elicited a mean tissue viability of 14.3 ± 2.7% and was predicted as irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
other: bovine
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
not required
Duration of treatment / exposure:
60 minutes
Number of animals or in vitro replicates:
No number given, multiple corneas used.
Irritation parameter:
in vitro irritation score
Value:
-1
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid

Results of control test

   Opacity +/- SD Permeability +/- SD

In Vitro Irritancy Score

 Irritant Classification
 Positive Control 245 +/- 7.371  2.118 +/- 0.111  276.8 +/- 7.6  Corrosive/Severe 
Negative Control    2.333 +/- 2.309 0. 009 +/- 0.001 N/A  N/A 
Interpretation of results:
GHS criteria not met
Conclusions:
Irritant classification non corrosive/non severe
Executive summary:

Further animal testing is not considered appropriate.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The substance was irritating to skin but not irritating to eyes during in vitro testing. The low water solubility will have reduced exposure to the surface of the excised eye used in the eye study, but otherwise, there is no clear reason why irritation to eyes appears less than to skin.

Justification for selection of skin irritation / corrosion endpoint:

The key study was conducted on the registered substance at a GLP accredited laboratory according to revised OECD Testing Guideline 404.

Justification for selection of eye irritation endpoint:

The study was conducted on the registered substance at a GLP accredited laboratory according to OECD Testing Guideline 437.

Effects on skin irritation/corrosion: moderately irritating

Justification for classification or non-classification

In vivo skin irritation testing allowed to demonstrate that the registered substance is not corrosive to the skin. In vitro irritation testing performed on the registered substance according to appropriate OECD Guidelines concluded that it meets the criteria for classification as irritant to the skin but not as damaging or irritant to the eye.