Registration Dossier

Administrative data

Description of key information

Historical skin irritation in-vivo and in-vitro testing demonstrated that the substance is of low irritancy and classification is not needed.
Historical in-vivo eye irritation demonstrated moderate effects and classification is required.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed to EU guidelines
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
GLP compliance:
yes (incl. certificate)
Details on test animals and environmental conditions:
In vitro study
Details on study design:
The principle of the assay is based on the measurement of cytotoxicity in reconstructed
human epidermal cultures following topical exposure to the test item by means of the
colourimetric MTT reduction assay. Cell viability is measured by enzymatic reduction of
the yellow MTT tetrazolium salt (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium
bromide) to a blue formazan salt (within the mitochondria of viable cells) in the test item
treated tissues relative to the negative controls.
Irritation / corrosion parameter:
other: other: In-vitro
Remarks on result:
other:
Remarks:
Basis: other: In-vitro. Remarks: In-vitro testing. (migrated information)
Irritant / corrosive response data:
The relative mean viability of the test item treated tissues was 112.6% after a 15-Minute exposure period.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The relative mean viability of the test item treated tissues was 112.6% after a 15-Minute exposure period and is not considered to be irritant to skin accordign to GHS criteria
Executive summary:

In view of the reported results being below thresholds for classification as irritant, it is considered unlikely that the diluted material manufactured and supplied (30 - 40% in water) will be irritating to skin.

It is not considered necessary to perform in-vivo testing on this substance in its concentrated form.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye 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 performed to valid methods
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The animals were in the weight range of 2.5 to 3.0 kg and approximately 11 to 13 weeks of age, prior to treatment (Day 1).
All rabbits were acclimatised to the experimental environment.
The rabbits were selected without conscious bias for the study.
They were housed individually in plastic cages with perforated floors
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed (pilot animal see Table 1).
Approximately 0.1 ml of the test substance was placed into the lower everted lid of one eye of each animal.
The eyelids were then gently held together for one second before releasing. The other eye remained untreated.
Observation period (in vivo):
Examination of the eyes was made after 1 hour and 1, 2, 3 (equivalent to 24, 48 and 72 hours after
instillation), 4, 7 and 14 days after instillation. Observation of the eyes was aided by the use of a handheld light.
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: Days 1- 3
Score:
ca. 2.5
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Positive response
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Days 1 - 3
Score:
ca. 0.3
Max. score:
1
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: Days 1 - 3
Score:
ca. 2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Positive response
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: Days 1 - 3
Score:
ca. 1.9
Max. score:
3
Reversibility:
fully reversible within: 14 days
Other effects:
Animals otherwise appeared healthy
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Due to corneal and conjunctival effects, using a mean of three animals at 24, 48 and 72 hour timepoints, the substance should be classified.
Proposed classification Eye Irrit 2
Executive summary:

The material tested was in the form as supplied at approximately 40%. As this gave a positive effect, further in-vivo testing at higher concentrations is not permitted for animal welfare reasons.

For in-vitro testing, solid materials need to be diluted to form fluid liquids and as this would mean testing solutions of 40% or lower, performing an in-vitro assay on this same concentration is not considered necessary.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Original in-vivo study was performed on diluted production grade material and was negative.

Justification for selection of eye irritation endpoint:
Valid study

Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Historical skin irritation in-vivo and in-vitro testing demonstrated that the substance is of low irritancy and classification is not needed. Historical in-vivo eye irritation demonstrated moderate effects and classification is required.