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Description of key information

Eye irritation:
Human Cornea Model Test:
Tissues of the human cornea model EpiOcular™were treated with the test item for 3, 30 and 60 minutes in duplicate. The cells for the negative control were treated for 60 min and the positive control for 15 and 45 min each in duplicate.
Compared with the result of the negative control, the relative absorbance values of the test item, corresponding to the cell viability, decreased after exposure to the cells. After the treatment period of 30 minutes, the cell viability was reduced to 22.0%, after 60 minutes only 16.1% of the cells survived. The 3-minutes exposure did not have any impact on the cell viability (103.7%).The calculated ET50-value was 20.7 minutes,consequently the test item was classified as moderate irritant.
BCOP-Test:The test item PPDA was brought onto the cornea of a bovine eye which had been incubated with cMEM without phenol red at 32 ± 1 °C for one hour and whose opacity had been measured. The test item was incubated on the cornea for 4 hours at 32 ± 1 °C. The test item PPDA showed no effects on the cornea of the bovine eye.
Skin irritation:
One valid experiment was performed.
Three tissues of the human skin model EpiDermTMwere treated with PPDA for 60 minutes.
In average, 24.5 mg of the solid test item (wetted with 25 µL DPBS-buffer) were applied to each tissue and spread to match the tissue size (0.63 cm2; as indicated by supplier).
DPBS-buffer was used as negative control, 5% SDS-solution was used as positive con-trol.
After treatment with the negative control, the absorbance values were within the required acceptability criterion of 1.0 < mean OD < 2.5. The positive control showed clear irritating effects. Variation within tissues was acceptable (< 18%).
After the treatment with the test item, the relative absorbance values were reduced to 93.8 %. This value is well above the threshold for irritation potential (50%).Therefore, PPDA is considered as not irritant in the Human Skin Model Test.

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:
2012-06-01 - 2012-09-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an internationally accepted guideline. All study parameters are based on the specific guideline.
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
other: human skin model EpiDermTM
Type of coverage:
open
Vehicle:
other: DPBS-buffer
Amount / concentration applied:
Tissue Amount
1 24.8 mg
2 25.0 mg
3 23.6 mg
Duration of treatment / exposure:
60 min.
Irritation / corrosion parameter:
other: other: % Formazan production
Value:
93.8
Remarks on result:
other:
Remarks:
Basis: mean. Time point: 60 min. Max. score: 100.0. Reversibility: no data. (migrated information)

Designation

PPDA

Positive Control

% Formazan production (Tissue 1)

93.4%

5.7%

% Formazan production (Tissue 2)

93.4%

6.0%

% Formazan production (Tissue 3)

94.7%

5.7%

% Formazan production Mean

93.8%

5.8%

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item is considered not irritant.
Executive summary:

One valid experiment was performed.

Three tissues of the human skin model EpiDermTMwere treated with PPDA for 60 minutes.

In average, 24.5 mg of the solid test item (wetted with 25 µL DPBS-buffer) were applied to each tissue and spread to match the tissue size (0.63 cm2; as indicated by supplier).

DPBS-buffer was used as negative control, 5% SDS-solution was used as positive control.

After treatment with the negative control, the absorbance values were within the required acceptability criterion of 1.0 < mean OD < 2.5. The positive control showed clear irritating effects. Variation within tissues was acceptable (< 18%).

After the treatment with the test item, the relative absorbance values were reduced to 93.8 %. This value is well above the threshold for irritation potential (50%). Therefore, PPDA is considered as

not irritant in the Human Skin Model Test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
2012-11-12 - 2012-12-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an internationally accepted guideline. All study parameters are based on the specific guideline.
Qualifier:
no guideline available
Guideline:
other: Human Cornea Model Test
GLP compliance:
yes (incl. QA statement)
Species:
other: Human Cornea Model
Vehicle:
water
Amount / concentration applied:
Each about 100 mg of the solid test item was applied to each of duplicate tissues, wetted with 30 µL of deionised water, and spread to cover the surface of the tissues evenly.
For the positive and negative controls 100 µL were dosed per tissue.
Duration of treatment / exposure:
3, 30 and 60 min.
Irritation parameter:
other: relative absorbance (%of negative control)
Run / experiment:
test item
Value:
16.1
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this study and under the experimental conditions reported, the test item PPDA possesses a moderate eye irritating potential.
Executive summary:

This in vitro study was performed to assess the eye irritation potential of PPDA by means of the Human Cornea Model Test.

Each about 100 mg of the solid test item was applied to each of duplicate tissues, wetted with 30 µL of deionised water, and spread to cover the surface of the tissues evenly.

100 µL of either the negative control (deionised water) or the positive control (0.3% Triton X-100) were applied to each tissue.

Tissues of the human cornea model EpiOcularwere treated with the test item for 3, 30 and 60 minutes in duplicate. The cells for the negative control were treated for 60 min and the positive control for 15 and 45 min each in duplicate.

After treatment with the negative control the absorbance values were well above the required acceptability criterion of mean OD≥0.8 for the60 minutestreatment interval thus showing the quality of the tissues.

Treatment with the positive control induced a decrease in the relative absorbance compared with the negative control to 64.5% (after 15 minutes treatment) or 26.3% (after 45 minutes treatment), respectively, thus ensuring the validity of the test system.

Compared with the result of the negative control, the relative absorbance values of the test item, corresponding to the cell viability, decreased after exposure to the cells. After the treatment period of 30 minutes, the cell viability was reduced to 22.0%, after 60 minutes only 16.1% of the cells survived. The 3-minutes exposure did not have any impact on the cell viability (103.7%).The calculated ET50-value was 20.7 minutes,consequently the test item was classified as moderate irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for selection of skin irritation / corrosion endpoint:
The GLP-study is reliable without restrictions.

Justification for selection of eye irritation endpoint:
The GLP-study is reliable without restrictions.

Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Skin irritation:

According to the CLP Regulation (EU GHS Regulation (EC) No 1272/2008) classification and labelling is not required for skin irritation of PPDA, based on reliable data from an in-vitro study according to OECD 439.

 

Eye irritation:

According to the CLP Regulation (EU GHS Regulation (EC) No 1272/2008) classification and labelling is required for eye irritation of PPDA, based on reliable data from two in-vitro studies in the Human Cornea Model Test and the BCOP-Test Since the substances has the potential to induce eye irritation a classification in Category 2 (irritating to eyes) is required. No corrosive properties of the test item were detected in the BCOP-Test.

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