Registration Dossier

Administrative data

Description of key information

The substance was found to be non-irritating to skin and eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Remarks:
in vitro
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
GLP compliance:
yes
Test system:
human skin model
Remarks:
reconstructed human epidermis EST-1000 (CellSystems, St. Katharinen, Germany)
Source species:
human
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: reconstructed human epidermis EST-1000 (CellSystems, St. Katharinen, Germany)
- Tissue batch number(s):
- Production date:
- Shipping date:
- Delivery date:
- Date of initiation of testing:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure:
- Temperature of post-treatment incubation (if applicable):

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps:
- Observable damage in the tissue due to washing:
- Modifications to validated SOP:

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration:
- Incubation time:
- Spectrophotometer:
- Wavelength:

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: The model used for this study has a functional stratum corneum with an underlying layer of living cells.
- Barrier function: The barrier function of the stratum corneum is adequate, as has been shown by the supplier.
- Morphology: The model used for this study has a functional stratum corneum with an underlying layer of living cells.
- Contamination:
- Reproducibility:

NUMBER OF REPLICATE TISSUES: 3

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to if the viability after 3 minutes exposure is less than 50% or if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is less than 15%.
- The test substance is considered to be non-corrosive to skin if the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour is greater than or equal to 15%.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL

NEGATIVE CONTROL
To check the reliability of this test procedure a blinded positive/negative control study is conducted at regular intervals in the lab. This reliability check is always performed by two technicians, two laboratories in parallel using the same batches of the control test items.
- Amount(s) applied (volume or weight):
- Concentration (if solution): 0.9% NaCl

POSITIVE CONTROL
To check the reliability of this test procedure a blinded positive/negative control study is conducted at regular intervals in the lab. This reliability check is always performed by two technicians, two laboratories in parallel using the same batches of the control test items.
- Amount(s) applied (volume or weight):
- Concentration (if solution):
Duration of treatment / exposure:
3 min and 60 min
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Remarks:
mean
Run / experiment:
test group 60 minutes exposure
Value:
98.72
Remarks on result:
other: % viability versus negative control group
Irritation / corrosion parameter:
% tissue viability
Remarks:
mean
Run / experiment:
test group 3 min exposure
Value:
102.95
Remarks on result:
other: % viability versus negative control group

 Sample No.  Test item  Time [min.]  % Viability
 1 -3  control NaCl 0.9%  60  100.00
 7 -9  Diethanolamine, propoxylated  60  98.72
 10 -12   control NaCl 0.9%  3  100.00
 16 -18  Diethanolamine, propoxylated  3  102.95

Diethanolamine, propoxylated was characterised by no significant impact on cell viability after 3 min. or after the 60 min. period.

Interpretation of results:
other: no corrosive property
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
other: EU Method B.46 (Skin Irritation)
GLP compliance:
yes
Test system:
human skin model
Remarks:
reconstructed human epidermis EST-1000 (CellSystems, St. Katharinen, Germany)
Source species:
human
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EST-1000 (CellSystems, St. Katharinen, Germany)
- Tissue batch number(s):
- Production date:
- Shipping date:
- Delivery date:
- Date of initiation of testing:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure:
- Temperature of post-treatment incubation (if applicable):

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps:
- Observable damage in the tissue due to washing:
- Modifications to validated SOP:

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration:
- Incubation time:
- Spectrophotometer:
- Wavelength:

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability: The model used for this study has a functional stratum corneum with an underlying layer of living cells.
- Barrier function: The barrier function of the stratum corneum is adequate, as has been shown by the supplier.
- Morphology: The model used for this study has a functional stratum corneum with an underlying layer of living cells.
- Contamination:
- Reproducibility::

NUMBER OF REPLICATE TISSUES: 3

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- An irritation potential of the test material according to UN GHS category 2 is predicted if the mean relative tissue viability of three individual tissues exposed to the test substance is less than or equal to 50% of the mean viability of the negative controls.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µL

NEGATIVE CONTROL
- Amount(s) applied (volume or weight):
- Concentration (if solution): 0.9 % NaCl

POSITIVE CONTROL
- Amount(s) applied (volume or weight):
- Concentration (if solution): 5% SDS (sodium dodecyl sulfate)
Duration of treatment / exposure:
20 minutes
Duration of post-treatment incubation (if applicable):
42 hours
Number of replicates:
3
Details on test animals or test system and environmental conditions:
The model used for this study has a functional stratum corneum with an underlying layer of living cells. The barrier function of the stratum corneum is adequate, as has been shown by the supplier.
Amount / concentration applied:
30 µl/insert (three replicates)
Irritation / corrosion parameter:
% tissue viability
Remarks:
mean
Run / experiment:
test group 20 minutes exposure, 42 h post-incubation
Value:
106.29
Remarks on result:
other: % versus negative control group
Irritation / corrosion parameter:
% tissue viability
Remarks:
mean
Run / experiment:
positive control 5% SDS
Value:
1.26
Remarks on result:
other: % versus negative control group

 Sample No.  Test item  % Viability
 1 -3  Negative Control NaCl 0.9%  100.00
 4 -6  Positive Control SDS 5%  1.26
 10 -12    Diethanolamine,propoxylated  106.29

Diethanolamine, propoxylated was characterised by no significant impact on cell viability.

Interpretation of results:
other: no skin irritation category as defined in the UN GHS
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
other: Crl: KBL(NZW)BR
Details on test animals or test system and environmental conditions:
according to guideline
sex of the test animals: female
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: The surrounding untreated skin served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after patch removal. If dermal irritation was observed, additional monitoring on day 7 and 14 after patch removal was done.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
Irritation parameter:
erythema score
Basis:
animal: #1-#3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1-#3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Other effects:
There were no systemic intolerance reactions.
Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
An acute dermal irritation/corrosion test (OECD 404) was performed with Diethethanolamine, propoxylated. No signs of dermal irritation were observed.
Executive summary:

An acute dermal irritation/corrosion test (OECD 404) was performed with Diethethanolamine, propoxylated. No signs of dermal irritation were observed.

According to classification criteria (CLP and DSD) Diethanolamine, propoxylated is not an irritant to the skin.

There were also no systemic intolerance reactions.

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
Study period:
July 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: according to OECD 405, including GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH
- Age at study initiation: circa 10 weeks
- Weight at study initiation: 2.5 - 2.6 kg
- Housing: single
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
Controls:
not required
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
24h
Observation period (in vivo):
1h, 24h, 48h and 72h after application in all 3 animals and on day 7 in 2 animals.
Number of animals or in vitro replicates:
3
Details on study design:
3 rabbits were dosed with 0.1 mL of Diethanolamine, propoxylated in the conjunctival sac of the right eyelid. Untreated left eyes served as negative control. Rabbits were observed at 1h, 24h, 48h, 72h and 7 days after application, with an otoscope lamp. Assessments were made regarding cornea opacity, affected area, conjunctivae redness, iris, chemosis and discharge. Scoring was based on the criteria of the OECD Harmonized Integrated Classification System.

A check for any dead or moribund animal was made twice each workday and once daily at weekends and on public holidays.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Remarks:
area involved
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: all
Score:
0.9
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Time point:
other: all
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
3
Irritant / corrosive response data:
Application of the test substance resulted in slight redness and chemosis of the conjunctivae, which were fully reversible within 72h.
Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, classification of Diethanolamine, propoxylated for eye irritation is not warranted.
Executive summary:

Previous to performing this in vivo eye irritation study, in vitro HET-CAM and BCOP (final report not yet available) assays were performed. In the HET-CAM test Diethanolamine, propoxylated elicited strong irritant effects. However, in the BCOP test, exposure to Diethanolamine, propoxylated did not cause eye irritation. In the in vivo study, 0.1 mL of Diethanolamine, propoxylated was applied to the eyes of 3 female rabbits. Only slight redness (mean score 0.9) and chemosis (mean score 0.7) of the conjunctivae was observed in all animals. This effects was fully reversible after 72h. Based on these results classification of Diethanolamine, propoxylated for eye irritation is not warranted.

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

Additional information

Skin irritation

Skin irritating properties of Diethanolamine, propoxylated was assessed using two in vitro and one in vivo assay.

Firstly, an in vitro test for skin corrosion was performed using a 3D skin model. Results indicated that Diethanolamine, propoxylated does not induce skin corrosion.

Secondly, an in vitro test for skin irritation was performed using a functional stratum corneum. Results from this study indicated that Diethanolamine, propoxylated does not cause skin irritation.

Thirdly, an in vivo test for acute skin irritation (OECD 404) was performed using 3 rabbits, which were exposed dermally to Diethanolamine, propoxylated. Results of this study indicated that Diethanolamine, propoxylated does not cause dermal irritation in rabbits.There were also no systemic intolerance reactions.

According to classification criteria Diethanolamine, propoxylated is not an irritant to the skin.

Eye irritation

In order to assess eye irritating effects of Diethanolamine, propoxylated, three tests were performed.

First, a HET-CAM test was carried out, which indicated that Diethanolamine, propoxylated induces strong irritant effects to the chorionallantoic membrane of hen eggs under the conditions of this assay.

As second in vitro test, a BCOP assay was performed. In this assay, Diethanolamine, propoxylated did not induce any eye irritation (currently, the report has not been finalised yet and it will be added to this dossier in a later stage).

Based on the results of the BCOP test, an in vivo test was performed, in which eyes of 3 rabbits were exposed to Diethanolamine, propoxylated. The results indicated that Diethanolamine, propoxylated is not an irritant to the eye.

According to classification criteria Diethanolamine, propoxylated is not an eye irritant.

Justification for classification or non-classification

Based on the results of a dermal irritation/corrosion study, classification of diethanolamine, propoxylated for skin irritation is not warranted in the EU.

Based on the results of an eye irritation/corrosion study, classification of diethanolamine, propoxylated for eye irritation

is not warranted in the EU.