Registration Dossier

Administrative data

Description of key information

Skin corrosion in vitro (OECD 431): not corrosive

Skin irritation / corrosion in vivo (OECD 404): not irritating

Eye irritation / serious eye damage in vivo (OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 Apr - 24 Apr 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Arbeit, Gesundheit und Soziales des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL(NZW)BR
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral untreated skin area of test animals served as control
Amount / concentration applied:
Amount: 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48, 72 h, 7 and 14 days after application
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approx. 2.5 x 2.5 cm
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing: treated skin area carefully washed with water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Other effects:
There were no systemic intolerance reactions.

Table 1: Iritant Effects on the Skin - (Exposure 3 min / 1 h)

Animal 1 (first animal)              

Observation (immediately after patch removal)       3 min       1 h

Erythema (redness) and eschar formation               0             0

Oedema formation                                                 0             0

Table 2: Irritant Effects on the Skin (Exposure: 4 h)

Animal 1, Body Weight 3.5 kg                                          

Observation (after patch removal)              1 h       24 h       48 h       72 h       7 days       14 days

Erythema (redness) and eschar formation    0         0         0        0         --        --

Oedema fomation                                    0         0         0         0        --        --

Animal 2, Body Weight 3.3 kg                                          

Observation (after patch removal)        1 h       24 h       48 h       72 h       7 days       14 days

Erythema (redness) and eschar formation    0        0        0     0        --         --

Oedema formation                                   0       0         0         0         --        --

Animal 3, Body Weight 3.2 kg                                          

Observation (after patch removal)        1 h       24 h       48 h       72 h       7 days       14 days

Erythema (redness) and eschar formation   0       0         0         0        --         --

Oedema formation                                     0         0        0         0        --        --

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
Ethane-1,2 -diol, propoxylated is not an irritant to the rabbit skin.
Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
3 Mar 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
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 (CeliSystems, St. Katharinen, Germany)
Source species:
human
Cell type:
non-transformed keratinocytes
Vehicle:
unchanged (no vehicle)
Control samples:
other: negative control: physiological saline solution (0.9 % NaCl)
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3 min
Value:
105.45
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
60 min
Value:
103.06
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

 Sample No.  Test item  Time [min.]  % Viability
 1 -3  control NaCl 0.9%  60  100.00
 4 -6  Ethan-1,2 -diol, propoxylated  60  103.06
 16 -18   control NaCl 0.9%  3  100.00
 19 -21   Ethan-1,2 -diol, propoxylated  3  105.45

Ethane-1 ,2-diol, propoxylated showed no significant impact on cell viability after 3 or 60 min.

Interpretation of results:
other: no corrosive property
Conclusions:
There is regulatory acceptance in the EU that a substance can be considered corrosive (Skin Corrosive Cat. 1, 1A, 1B/C) based on a positive result in the Reconstructed human epidermis test method (in vitro skin corrosion). A negative in vitro corrosivity response is not conclusive with respect to non-classification or classification as a skin irritant and therefore requires further evaluation and/or data generation.
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:
29 Apr - 8 May 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Arbeit, Gesundheit und Soziales des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Species:
rabbit
Strain:
New Zealand White
Remarks:
Crl:KBL(NZW)BR
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: female
- Source: Charles River, Kißlegg, Germany
- Age at study initiation: adult
- Weight at study initiation: 2300-2700 g
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 25
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
other: one untreated eye of test animals served as control
Amount / concentration applied:
0.1 mL

Duration of treatment / exposure:
24 h
Observation period (in vivo):
1, 24, 48, 72 h post application. If no irritation indices were observed after 72 h, the study was finished. If eye irritation was observed, animals were monitored usually on day 7, 14 and 21 after application until the changes had completely subsided, however for not more than 21 days after application
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: The eye was not rinsed for at least 24 h following instillation

SCORING SYSTEM: Draize
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 3 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Other effects:
There were no systemic intolerance reactions.

A summary of the individual scores is attached below under 'Attached background material'.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
Ethane-1,2 -diol, propoxylated resulted in slight irritation of the skin of rabbit, which was fully reversible within 72 h.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

The skin irritation potential of ethane-1,2-diol, propoxylated (CAS No.31923-84-9, EC No. 500-078-0) was investigated in an in vivo study performed according to OECD guideline 404 under GLP conditions (rel 1-key, rabbit, OECD 404, Bayer Schering Pharma, 2009c, T7079830). 0.5 mL of the unchanged test substance was applied to the shaved skin of three New Zealand White (Crl:KBL(NZW)BR) rabbits under semi-occlusive conditions. Due to the unknown irritant potential of the test substance, in a first step only one animal was used and three test patches were applied successively to this animal. The first patch was removed after 3 minutes. As no serious skin reactions were observed, the second patch was applied and removed after 1 h. The observations indicated the absence of adverse skin reactions and, therefore, the third patch was applied and removed after 4 h. The test was completed using two additional animals, exposed for 4 h. Skin reactions were scored 1, 24, 48 and 72 h after removal of the patches. No skin reactions were observed for any animal at any reading time point. Due to the absence of skin reactions, the test was terminated after the 72 h reading and ethane-1,2-diol, propoxylated was considered not irritating to the skin.

The findings of the in vivo study are supported by the results of an in vitro skin corrosion test conducted according to OECD guideline 431 under GLP conditions (rel 1-supp, in vitro skin corrosion, OECD 431, Bayer Schering Pharma, 2009d, T8079417). In this in vitro study, ethane-1,2-diol, propoxylated (CAS No.31923-84-9, EC No. 500-078-0) was applied to a reconstructed human epidermis for detection of topically applied skin corrosives. Corrosive skin effects are defined as irreversible damage of skin following the application of a test substance for up to 4 h. The unchanged test substance was applied to the epidermal equivalents in triplets. For the determination of time related cytotoxic effects the incubation periods were 3 and 60 min. To check the reliability of this test procedure a blinded positive/negative control study is conducted at regular intervals at the testing facility. The % cell viabilities determined after 3 and 60 min were 105.45 and 103.06%, respectively. In conclusion, ethane-1,2-diol, propoxylated did not exhibit corrosive properties in this in vitro skin corrosivity test.

Eye irritation / serious eye damage

Ethane-1,2-diol, propoxylated (CAS No.31923-84-9, EC No. 500-078-0) was examined for its eye irritation potential in an in vivo study performed according to OECD guideline 405 under GLP conditions (rel 1-key, rabbit, OECD 405, Bayer Schering Pharma, 2009e, T8079831). 0.1 mL of the pure liquid test substance was instilled into the conjunctival sac of one eye of a first New Zealand White (Crl:KBL(NZW)BR) rabbit after having gently pulled the lower lid away from the eyeball. The other eye, which remained untreated, served as control. The eye was rinsed approximately 24 h following instillation. Since no severe signs of irritation were noticed after 1 h, two further animals were included in the test and treated similar to the first one. Eye reaction was scored according to the Draize scheme approx. 1, 24, 48 and 72 h post application. Since no eye irritation was observed 72 h post application, the study was terminated. Application of the test substance had no effect on corneal opacity, iris and chemosis scores (all 0 for all animals at all reading time points). Only slight conjunctival redness was observed 24 and 48 h after instillation (24/48/72 h mean scores 1 for two animals and 0.66 for the third animal). All effects had completely reversed at the 72 h reading. Based on the minimal effects observed in this in vivo study, ethane-1,2-diol, propoxylated is considered not irritating to eyes.

Justification for classification or non-classification

The available data on skin and eye irritation with ethane-1,2-diol, propoxylated (CAS No.31923-84-9, EC No. 500-078-0) do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.