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Description of key information

The test item is not considered to possess an irritant potential to the skin according to results of an in vitro test conducted with reconstructed human epidermis.

The test item is not considered to possess an irritant potential to the eye according to results of an in vitro HET-CAM 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:
June 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to: OECD Guideline for the Testing of Chemicals, Draft Proposal for a New Guideline, In Vitro Skin Irritation: Reconstructed Human Epidermis (RhE) Test Method, 11 December 2009, Vers. 4
Qualifier:
according to guideline
Guideline:
other: OECD Guideline for the Testing of Chemicals, Draft Proposal for a New Guideline, In Vitro Skin Irritation: Reconstructed Human Epidermis (RhE) Test Method, 11 December 2009, Vers. 4
GLP compliance:
yes (incl. QA statement)
Test system:
human skin model
Remarks:
EpiSkin
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
skin obtained from plastic surgery from multiple donors
Source strain:
not specified
Vehicle:
unchanged (no vehicle)
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
10 µL
Duration of treatment / exposure:
15 min
Duration of post-treatment incubation (if applicable):
42 h
Number of replicates:
3
Irritation / corrosion parameter:
other: Mean rel. MTT absorbance
Run / experiment:
15 min treatment
Value:
104.3
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
100.0
Positive controls validity:
valid
Remarks:
9.5
Other effects / acceptance of results:
After treatment with the test item SAT 090073 the mean relative absorbance value did not decrease (104.3%) compared to the negative control. Therefore, the test item is not considered to possess an irritant potential.

Optical evaluation of the MTT-reducing capacity of the test item after 1 hour incubation with MTT-reagent did not show blue colour.

Table 1: Results after treatment with SAT 090073

 

Dose group

Treat-ment Interval

Absorbance 570 nm
Tissue 1*

Absorbance 570 nm
Tissue 2*

Absorbance 570 nm
Tissue 3*

Mean Absorbance of 3 Tissues

Standard Deviation of 3 Tissues

Rel. Absorbance

[% of Negative Control]**

Standard Deviation [%]

Negative Control

15 min

0.857

0.936

0.896

0.896

0.039

100.0

4.4

Positive Control

15 min

0.061

0.087

0.107

0.085

0.023

9.5

2.6

SAT 090073

15 min

0.988

0.902

0.916

0.935

0.046

104.3

5.1

 *       Mean of two replicate wells after blank correction
**
      relative absorbance [rounded values]:

After treatment with the test item SAT 090073 the mean relative absorbance value did not decreas (104.3%) compared to the negative control. This value is well above the threshold for irritancy of 50%. Therefore, the test item is not considered to possess an irritant potential.

Interpretation of results:
GHS criteria not met
Conclusions:
In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item SAT 090073 is not irritant to skin.
Executive summary:

This in vitro study was performed to assess the irritation potential of SAT 090073 by means of the Human Skin Model Test.

Three tissues of the human skin modelEpiSkin™ were treated with the test item, the negative or the positive control for 15 minutes.

Approximately 10 µL of the neat test item were applied to each tissue and spread to match the tissue size.

10 µL of either the negative control (deionised water) or the positive control (5% Sodium lauryl sulfate) were applied to each tissue.

After treatment with the negative control the absorbance values were well within the required acceptability criterion of mean OD 0.6 and ≤ 1.5 for the15 minutes treatment interval thus showing the quality of the tissues and the specific batch of the tissue model.

Treatment with the positive control induced a decrease in the relative absorbance as compared to the negative control to 9.5% thus ensuring the validity of the test system.

The standard deviations between the % variabilities of the test item, the positive and negative controls were below 18% thus ensuring the validity of the study.

The control values are well in the range of our historical data.

After treatment with the test item SAT 090073 the mean relative absorbance value did not decrease (104.3%) compared to the negative control. Therefore, the test item is not considered to possess an irritant potential.

According to the current prediction model no classification and labeling of SAT 090073 is necessary with respect to skin irritation under EU and UN classification.

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:
June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to: INVITTOX Protocol No. 47: HET-CAM Test.
Qualifier:
according to guideline
Guideline:
other: INVITTOX Protocol No. 47: HET-CAM Test. http://ecvam-sis.jrc.it
GLP compliance:
yes (incl. QA statement)
Species:
other: HET-CAM
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
Approx. 100 mg of the neat test item were applied onto the CAM
Duration of treatment / exposure:
5 min
Details on study design:
Approx. 100 mg of the neat test item were applied onto the CAM in order to cover at least 50% of the CAM. The CAM was exposed to the test item for 5 minutes. During this 5 minutes reactions on the blood vessels in and under the CAM in close proximity to the test item were monitored. The CAMs of three eggs were treated with the test item. In addition to the test item a negative control (0.9% NaCl w/v)), two positive controls (1% SDS solution in deionised water and 0.1 N NaOH), and a reference item (5% (w/v) Texapon) were tested.
Irritation parameter:
in vitro irritation score
Run / experiment:
Mean (5 min. exposure)
Value:
0
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid

Table 1: Results with SAT 090073, as well as negative and positive controls, and the reference item


Test Group

Time until Haemorrhage [s]

Time until Lysis [s]

Time until Coagulation [s]

Irritancy Index

Mean Irritancy Index

Negative Control

301

301

301

0.00

0.00

301

301

301

0.00

301

301

301

0.00

Positive Control

0.1 N NaOH

10

45

17

19.34

19.26

9

41

16

19.48

11

57

20

18.96

Positive Control

1% SDS

13

30

301

11.12

11.11

14

28

301

11.15

14

32

301

11.06

Reference Item 5% AS Texpon

17

35

301

10.94

10.78

22

47

301

10.58

20

38

301

10.82

Test Item

301

301

301

0.00

0.00

301

301

301

0.00

301

301

301

0.00

Mean irritancy index of 3 eggs: Test Item = 0.00

Mean irritancy index of 3 eggs: Positive Control (Sodium dodecyl sulphate) = 11.11

                                                        Positive Control (Sodium hydroxide solution) = 19.26

                                                        Reference Item (Texapon) = 10.78

Interpretation of results:
GHS criteria not met
Remarks:
other: INVITTOX Protocol No. 47: HET-CAM Test. http://ecvam-sis.jrc.it
Conclusions:
In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item SAT 090073 does not possess any irritating potential.
Executive summary:

This in vitro study was performed to assess the irritating potential of SAT 090073 by detection of damages in blood vessels under the chorioallantoic membrane of 9 day incubated chicken eggs.

Each 300 µL of the test item, the positive and the negative controls, and the reference item were applied to three eggs each such that at least 50 % of the membrane was covered. During the observation period for 300 seconds any lesions in close proximity to the covered membrane were monitored and recorded. The observation time was 5 minutes at room temperature.

Physiological sodium chloride solution (0.9 % (w/v) in deionised water) was used as negative control.

The negative control showed no irritating effect on the blood vessels under the membrane. The irritancy mean index is 0.00.

A 1 % solution of SDS and 0.1 NaOH were used as positive controls.

The positive controls induced a severe irritation on the blood vessels. The calculated mean irritancy indices are 11.11 for 1 % SDS and 19.26 for 0.1 N NaOH. The reference itemTexapon ASV Spezial (5 % AS) was chosen because of its known eye irritating properties and induced a severe irritation on the blood vessels. The calculated mean irritancy index is 10.78.

The mean irritancy indices of the controls are well comparable with the historical control values and are within the acceptance criteria. The result of the reference item demonstrated a correct interpretation. Therefore, it was concluded that the test was valid.

No irritating effects were observed during 5 min incubation with SAT 090073. The calculated irritancy mean index is 0.00.

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

Additional information

After having registered Sa 57 for the tonnage band 1 – 10 to, we now want to increase the production volume and therefore want to register Sa 57 for the tonnage band 10 – 100 to. Since products incorporating Sa 57 are intended to have direct contact with end consumers, prior to initiating any new test we have defined potential genotoxic properties as knock-out criterion. In case of genotoxic properties we would stop using the material and consequentially cease the registration which would not affect any other registrant since Sa 57 is proprietary to Henkel. In this case, there would be no need anymore to generate more data in order to support such a registration. From our perspective this approach is the best solution from an economical as well as from an animal welfare point of view. In that respect, we have developed a testing strategy for obtaining the toxicological data required for the 10 – 100 to tonnage band. This testing strategy applies a tiered approach starting with the two required in vitro genotoxicity assays – gene mutation and chromosome aberration in mammalian cells. Any other test will only be initiated if genotoxicity is finally clarified.  As described in this dossier, Sa 57 is not considered clastogenic even though some uncertainty remains with regard to its potential ability to disturb mitotic processes. There are conflicting data concerning the gene mutation potential from an assay with bacteria and another assay in mammalian cells. We consider these in vitro findings to be initial results which need further clarification. In Annex VIII of the REACH legislation it is stated that  “… appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII…”. In order to clarify the available in vitro results with regard to their relevance in vivo, we therefore proposed to conduct in vivo genotoxicity testing as outlined in section 7.6.2. This test was completed only recently. Toxicological data other than the mentioned genotoxicity results required for the tonnage band of 10 - 100 to are therefore not yet available but will be generated and provided as soon as possible.

Justification for classification or non-classification

Based on available in vitro test data, no skin or eye irritation is to be expected. Therefore, the classification criteria are not met.

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