Registration Dossier

Administrative data

Description of key information

skin irritation (OECD 439): irritating
eye irritation (OECD 405): highly irritating / corrosive
SCLs according to GHS:
>=5% - <10% Eye Irrit. Cat.2
< 5% No Classification

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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:
guideline study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
(2010)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit
Details on study design:
An in-vitro study with the EpiDermTM human skin model comprising a reconstructed epidermis with a functional stratum corneum was performed. The EpiDermTM tissues were obtained by MatTek. The tissue was moistened with 25 µL DPBS (Dulbecco`s Phosphate Buffered Saline) to ensure good skin contact before 25 mg of the test substance were applied directly atop the EpiDermTM tissue. DPBS was used as negative control while 5% SDS (Sodium dodecyl sulfate) was used as positive control. A total of 3 tissues per dose group were used in duplicate. Irritation properties of the test substance are identified by the decrease of cell viability after exposure as determined by using the MTT reduction assay.
The tissues were maintained at 37 °C in humidified atmosphere (5% CO2/95% air). All media used during the study (for instance the incubation medium and MTT medium) were pre-warmed. After treatment, tissues were incubated at 37 °C in humidified atmosphere for 35 min and placed at room temperature thereafter. After 60 min the tissues were washed with DPBS, placed in pre-warmed incubation medium and were further incubated for 24 h at 37 °C in humidified atmosphere. After a medium change the tissues were incubated for additional 18 h prior to incubation in MTT medium for 3 h. After incubation in MTT the tissues were three times rinsed with DPBS before extraction of the reduced MTT with isopropanol for 2 hours. Per each tissue two aliquots of the extract were transferred into 96-well plates and analysed in a plate spectrophotometer.
The MTT reducing potential and the coloring potential of the test substance as possible confounding factors were assessed.
A test substance is concluded to be irritating if the relative mean tissue viability after 60 minute exposure and 42 hours post-treatment incubation is below 50%.
Irritation / corrosion parameter:
other: other: viability of treated tissue (in % of control)
Value:
6.8
Remarks on result:
other:
Remarks:
Basis: mean all tissued. Time point: 60 min. Max. score: 100.0. Reversibility: other: not applicable. Remarks: A test substance is considered to be irritating if the viability after 60 minutes is at or below 50%.. (migrated information)
Irritant / corrosive response data:
The test item showed irritating potential. However, only two experiments with test item treated tissues instead of three were evaluated due to loss of one tissue during washing. As each experiment was performed in duplicate 4 tissues were assessed. The test mets the acceptance criteria (for details see any other information on results).

Table 1: Summary of results

Test group

n

Treatment period (min)

Mean OD550value

Viability (%)

Mean inter tissue viability difference (%)

Negative control

3

60

1.78

100

15.8

Test item

2*

60

0.12

6.8

0.8

Positive control

3

60

0.12

6.6

0.9

* Only two test item treated tissues instead of three were evaluated due to loss of one tissue during washing.

The test meets acceptance criteria if:

Mean OD of the three negative control tissues is above≥ 1 and ≤2.5

Mean relative tissue viability of the three positive controls is at or below 20%,

The maximum inter tissue viability difference (determined as SD) between tissues treated identically is at or below 18%.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
CLP: Skin irrit 2, H315
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Details on study design:
An in-vitro study with the EpiDermTM human skin model comprising a reconstructed epidermis with a functional stratum corneum was performed. The EpiDermTM tissues were obtained by MatTek. The tissue was moistened with 25 µL DPBS (Dulbecco`s Phosphate Buffered Saline) to ensure good skin contact before 25 mg of the test substance were applied directly atop the EpiDermTM tissue. DPBS was used as negative control while 5% SDS (Sodium dodecyl sulfate) was used as positive control. A total of 3 tissues per dose group were used in duplicate. Irritation properties of the test substance are identified by the decrease of cell viability after exposure as determined by using the MTT reduction assay.
The tissues were maintained at 37 °C in humidified atmosphere (5% CO2/95% air). All media used during the study (for instance the incubation medium and MTT medium) were pre-warmed. After treatment, tissues were incubated at 37 °C in humidified atmosphere for 35 min and placed at room temperature thereafter. After 60 min the tissues were washed with DPBS, placed in pre-warmed incubation medium and were further incubated for 24 h at 37 °C in humidified atmosphere. After a medium change the tissues were incubated for additional 18 h prior to incubation in MTT medium for 3 h. After incubation in MTT the tissues were three times rinsed with DPBS before extraction of the reduced MTT with isopropanol for 2 hours. Per each tissue two aliquots of the extract were transferred into 96-well plates and analysed in a plate spectrophotometer.
The MTT reducing potential and the coloring potential of the test substance as possible confounding factors were assessed.
A test substance is concluded to be irritating if the relative mean tissue viability after 60 minute exposure and 42 hours post-treatment incubation is below 50%.
Irritation / corrosion parameter:
other: other: viability of treated tissue (in % of control)
Value:
6.8
Remarks on result:
other:
Remarks:
Basis: mean all tissued. Time point: 60 min. Max. score: 100.0. Reversibility: other: not applicable. Remarks: A test substance is considered to be irritating if the viability after 60 minutes is at or below 50%.. (migrated information)
Irritant / corrosive response data:
The test item showed irritating potential. However, only two experiments with test item treated tissues instead of three were evaluated due to loss of one tissue during washing. As each experiment was performed in duplicate 4 tissues were assessed. The test mets the acceptance criteria (for details see any other information on results).

Table 1: Summary of results

Test group

n

Treatment period (min)

Mean OD550value

Viability (%)

Mean inter tissue viability difference (%)

Negative control

3

60

1.78

100

15.8

Test item

2*

60

0.12

6.8

0.8

Positive control

3

60

0.12

6.6

0.9

* Only two test item treated tissues instead of three were evaluated due to loss of one tissue during washing.

The test meets acceptance criteria if:

Mean OD of the three negative control tissues is above≥ 1 and ≤2.5

Mean relative tissue viability of the three positive controls is at or below 20%,

The maximum inter tissue viability difference (determined as SD) between tissues treated identically is at or below 18%.

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
CLP: Skin irrit 2, H315
Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Details on study design:
An in-vitro study with the EpiDermTM human skin model comprising a reconstructed epidermis with a functional stratum corneum was performed. The EpiDermTM tissues were obtained by MatTek. 25 mg of the test substance were applied directly atop the EpiDermTM tissue. The test substance was moistened with 25 µL water to ensure good skin contact. Distilled water was used as negative control while 8 N KOH was used as positive control. A total of 4 tissues per dose group and 2 replicates per treatment period (3 and 60 minutes) were used. Corrosive properties of the test substance are identified by the decrease of cell viability after exposure as determined by using the MTT reduction assay.
The tissues were maintained at 37°C in humidified atmosphere (5% CO2/95% air) and maintenance during preparation and treatment was appropriate. All media used during the study (for instance the incubation medium and MTT medium) were pre-warmed. Tissues were rinsed with PBS before incubating in MTT medium for 3 h at 37°C in humidified atmosphere. After incubation in MTT the tissues were again rinsed with PBS before extraction of the reduced MTT with isopropanol for 2 hours in sealed bags. Per each tissue three aliquots of the extract were transferred into 96-well plates and analysed in a plate spectrophotometer.
The MTT reducing potential and the coloring potential of the test substance as possible confounding factors were assessed.

A test substance is concluded to be non-corrosive if the relative mean tissue viability after 3 minute treatment is above 50% and above 15% after 60 minutes.

The test meets acceptance criteria if:
Mean OD of the two negative control tissues of the 3 and 60 minute treatment period is at or above 0.8,
Mean relative tissue viability of the two positive controls of the 3 minute treatment period is at or below 30%,
The maximum inter tissue viability difference between tissues treated identically is at or below 30%.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3 min
Value:
84
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: A test substance is considered to be corrosive if the viability after 3 minutes is at or below 50%.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
60 min
Value:
48
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: A test substance is considered to be corrosive if the viability after 60 minutes is at or below 15%.
Other effects / acceptance of results:
The test item showed no corrosive potential. The test mets the acceptance criteria (for details see any other information on results).

Table 1: Summary of results

Test group

Treatment period (min)

Mean OD550value

Viability (%)

Mean inter tissue viability difference (%)

Negative control

3

2.12

100

8.3

Test item

3

1.781

84

24.3

Positive control

3

0.355

17

15.1

Negative control

60

2.174

100

0.8

Test item

60

1.036

48

23.8

Positive control

60

0.204

9

18.7

The mean OD value of the two negative control tissues of the 3 and 60 minute treatment period is above 0.8. The mean relative tissue viability of the two positive controls of the 3 minute treatment period is below 30%. The maximum inter tissue viability difference between tissues treated identically is below 30%.

Interpretation of results:
other: non-corrosive
Remarks:
Criteria used for interpretation of results: EU
Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Version / remarks:
(2004)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit
Details on study design:
An in-vitro study with the EpiDermTM human skin model comprising a reconstructed epidermis with a functional stratum corneum was performed. The EpiDermTM tissues were obtained by MatTek. 25 mg of the test substance were applied directly atop the EpiDermTM tissue. The test substance was moistened with 25 µL water to ensure good skin contact. Distilled water was used as negative control while 8 N KOH was used as positive control. A total of 4 tissues per dose group and 2 replicates per treatment period (3 and 60 minutes) were used. Corrosive properties of the test substance are identified by the decrease of cell viability after exposure as determined by using the MTT reduction assay.
The tissues were maintained at 37°C in humidified atmosphere (5% CO2/95% air) and maintenance during preparation and treatment was appropriate. All media used during the study (for instance the incubation medium and MTT medium) were pre-warmed. Tissues were rinsed with PBS before incubating in MTT medium for 3 h at 37°C in humidified atmosphere. After incubation in MTT the tissues were again rinsed with PBS before extraction of the reduced MTT with isopropanol for 2 hours in sealed bags. Per each tissue three aliquots of the extract were transferred into 96-well plates and analysed in a plate spectrophotometer.
The MTT reducing potential and the coloring potential of the test substance as possible confounding factors were assessed.

A test substance is concluded to be non-corrosive if the relative mean tissue viability after 3 minute treatment is above 50% and above 15% after 60 minutes.

The test meets acceptance criteria if:
Mean OD of the two negative control tissues of the 3 and 60 minute treatment period is at or above 0.8,
Mean relative tissue viability of the two positive controls of the 3 minute treatment period is at or below 30%,
The maximum inter tissue viability difference between tissues treated identically is at or below 30%.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3 min
Value:
84
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: A test substance is considered to be corrosive if the viability after 3 minutes is at or below 50%.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
60 min
Value:
48
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: A test substance is considered to be corrosive if the viability after 60 minutes is at or below 15%.
Other effects / acceptance of results:
The test item showed no corrosive potential. The test mets the acceptance criteria (for details see any other information on results).

Table 1: Summary of results

Test group

Treatment period (min)

Mean OD550value

Viability (%)

Mean inter tissue viability difference (%)

Negative control

3

2.12

100

8.3

Test item

3

1.781

84

24.3

Positive control

3

0.355

17

15.1

Negative control

60

2.174

100

0.8

Test item

60

1.036

48

23.8

Positive control

60

0.204

9

18.7

The mean OD value of the two negative control tissues of the 3 and 60 minute treatment period is above 0.8. The mean relative tissue viability of the two positive controls of the 3 minute treatment period is below 30%. The maximum inter tissue viability difference between tissues treated identically is below 30%.

Interpretation of results:
other: non-corrosive
Remarks:
Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.6
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
GHS criteria not met
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Vehicle:
water
Controls:
not required
Amount / concentration applied:
Amount: 0.1 mL
Concentration: 20% (5.4% a.i.)
Duration of treatment / exposure:
single administration without washing
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.2
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
4
Interpretation of results:
GHS criteria not met
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
5% a.s.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Only limited data on test material are available.
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
Study was conduced before implementation of GLP.
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.6
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Only limited data on test material are available.
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
Study was conduced before implementation of GLP.
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
n.a.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Interpretation of results:
GHS criteria not met
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Vehicle:
water
Controls:
not required
Amount / concentration applied:
Amount: 0.1 mL
Concentration: 20% (5.4% a.i.)
Duration of treatment / exposure:
single administration without washing
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
1.2
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24+48+72 h
Score:
0
Max. score:
4
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No data regarding the skin and eye irritating properties of AES (C8-10) Na (CAS 68891-29-2) is available. Therefore the endpoint skin irritation is covered by read across to structurally related AES, i.e. AES (C8-10) Na. With regard to the endpoint eye irritation AES (C8-10) Na (CAS 68891-29-2) is classified as worst case scenario according to the classification criteria of Regulation (EC) No. 1272/2008 as Eye Dam.1, H318. However, to assess specific concentration limits (SCL) for eye irritation a read across to structurally related AES, i.e. AES (C12-14, 1-2.5 EO)Na (CAS 68891-38-3) and AES (C10-16, 1-2.5 EO)Na (CAS68585-34-2) was performed. The AES reported within the AES category show similar structural, physico-chemical, environmental and toxicological properties. The approach of grouping different AES for the evaluation of their effects on human health and the environment was also made by the Danish EPA (2001) and HERA (2003), supporting the read across approach between structurally related AES

Within the HERA report (2003) it was concluded that “The skin irritating properties of AES normally decrease with increasing level of ethoxylation.” Therefore read across was performed to AES with an ethoxylation grade of 1 - 2.5 reflecting the ethoxylation grade of Na C8-10 AES (CAS 68891-29-2).

 

There are two studies for the read-across substance AES (C8-10) Na addressing skin irritation available.

One in vitro study was performed according to OECD Guideline 431 to assess the skin corrosive potential of AES (C8-10, 2 EO)Na. 25 mg of the test substance was applied atop an EpiDerm ™ tissue, comprising of a reconstructed epidermis with a functional stratum corneum, for 3 and 60 minutes (Z&S, 2012c). The viability of the treated tissue, as assessed via the MTT assay, was 84% of control after 3 min exposure and 48% of control after 60 min exposure period. Thus, AES (C8-10, 2 EO)Na was not corrosive.

The second study was performed according to OECD Guideline 439 with AES (C8-10, 2 EO)Na. 25 mg of the test substance was applied atop an EpiDerm ™ tissue, comprising of a reconstructed epidermis with a functional stratum corneum, for 60 minutes (Z&S, 2012d). The viability of the treated tissue, as assessed via the MTT assay, was 7% of control after 60 min exposure. Thus, AES (C8-10, 2 EO)Na was irritating.

Data on eye irritation:

As worst case scenario AES (C8-10) NH4 (CAS 68891-29-2) is classified according to the classification criteria of Regulation (EC) No. 1272/2008 as Eye Dam.1, H318. However, as corrosion and irritation depends on the concentration of the substance in a solvent, further studies with lower concentrations of the test substance were also considered to assess whether specific concentration limits can be set. For this purpose, two studies with AES (C12-14, 4 EO)Na (CAS 68891-38-3) and two studies with AES (C10-16, 2 EO)Na (CAS68585-34-2) with a concentration range of 1 to 10% were evaluated.

One study was performed with 0.1 mL AES (C12-14, 4 EO)Na (CAS 68891-38-3, analytical purity 10%) similar to OECD guideline 405 (Stepan 1980a) on three New Zealand White rabbits with an observation period of 7 days. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 1.6, 0.6, 2 and 1.6 representing an eye irritating effect of the test substance at a concentration of 10%. The effects were not fully reversed within the 7 days observation period. Therefore the test substance showed eye irritating potential.

The second study was performed with 0.1 mL AES (C12-14, 4 EO)Na (CAS 68891-38-3) similar to OECD guideline 405 (Stepan, 1980b) on three New Zealand White rabbits with an observation period of 7 days, however at an concentration of 5%. The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 0.4, 0, 1 and 0.3. All effects reversed within the 7 days observation period. Thus, the test substance was not irritating to the eye at a concentration of 5%.

In a further supporting study with AES (C12-14, 2 EO)Na ( CAS 68891-38-3, analytical purity 27%) according to OECD guideline 405, 0.1 mL of the test substance was applied to the rabbits eye at a concentration of 20% resulting in an actual concentration of 5.4% (Z&S, 1997). The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 0, 0, 1.2 and 0. The conjunctival redness reversed within the 7 days observation period. Thus the test substance was not irritating to eyes at a concentration of 5.4 %.

The supporting study with AES (C10-16)Na (CAS 68585-34-2, no data on grade of ethoxylation, analytical purity 58%) was performed similar to OECD guideline 405 (Unilever, 1980). The mean (24, 48 and 72 h reading) cornea, iris, conjunctivae and chemosis scores over all animals were 0.7, 1, 3 and 3.3. All findings were fully reversible within the observation period. Thus, the test substance showed eye irritating properties at a concentration of 5%.

Based on the above mentioned results with different concentrations of structurally related alkyl ether sulfates a cut of value for classification as severe irritating to eyes is set at a concentration of 10% and for classification as irritating at a concentration of 5% for the AES of the category.

 

References:

Danish EPA - Environmental and Health Assessment of Substances in Household Detergents and Cosmetic Detergent Products (2001). Environmental Project No. 615, pp. 24-28

HERA (2003). Human & Environmental Risk Assessment on ingredients of European household cleaning products Alcohol Ethoxysulphates, Human Health Risk Assessment Draft, 2003. http: //www. heraproject. com.

Justification for classification or non-classification

According to the classification criteria of Regulation (EC) No. 1272/2008 the test substance needs to be classified with Skin Irrit. 2, H315 and Eye Dam.1, H318.

It could be shown with experimental data on eye irritation that below 10% active substance only the classification Eye Irrit. Cat.2 remains and below 5% active substance no classification at all is necessary. Hence, the Generic Concentration Limits (GCLs) can be substituted by the mentioned specific ones (SCLs).