Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

No irritating or corrosive property to skin of the test item was determined by the two 3D skin models used (Wingenroth, 2010).

The irritant / corrosive potential of the test substance was studied on the skin of rabbits. The method used complied with the OECD - Guideline for Testing of Chemicals No. 404 -" Acute Dermal Irritation/Corrosion"; adopted: 24th April 2002 and the EEC Directive No. 440/2008 Part B - Method BA. According to classification criteria the test substance is not an irritant to the skin (Gmelin, 2010).

The test substance  was identified as "non irritant" to the Chorioallantoic membrane (Irritation Score (IS) = O)in a HET-CAM assay (Wingenroth, 2010).  

The irritant / corrosive effects of the test substance were tested on the eye of female New Zealand White rabbits. The method used complied with the OECD - Guideline for Testing of Chemicals No. 405 -"Acute Eye Irritation/Corrosion"; adopted: 24th April 2002 and EEC Directive No. 440/2008 Part B - Method B.5. According to classification criteria the test substance causes serious damage to eyes with full reversibility within 14 days (Gmelin, 2011).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Preparation of test site:
other: On the day before the test, the fur was shorn on the right and left side from the dorso-lateral area of the trunk of each of the rabbits. Care was taken to avoid abrading the skin. Only animals with healthy and intact skin were used.
Controls:
other: The surrounding untreated skin served as control.
Duration of treatment / exposure:
Due to a possible irritant potential of the test substance, in the first step only one animal was used and three test patches were applied successively to this animal, as described above. The first patch was removed after three minutes. As no serious skin reactions were observed, the second patch was applied and removed after one hour. At this stage the observations indicated that with respect to animal welfare the exposure can be allowed to extend to four hours, therefore the third patch was applied and removed after four hours and the responses were graded one hour later.
The test was completed using two additional animals, exposed for four hours.
Observation period:
Based on most recent guidelines the dermal irritation was scored approximately at 1, 24, 48 and 72 hours after patch removal. If no irritation indices were observed, after 72 h, the study was finished. If dermal irritation was observed, animals were monitored usually on day 7 and 14 after patch removal until the changes had completely subsided, however for not more than 14 days after application.
Number of animals:
Three animals were used for the study.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 1d
Irritation parameter:
edema 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:
edema 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
Reversibility:
fully reversible within: 1d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4

Summary of Irritant Effects (Score)

 Animal  Effect  24 h  48 h  72h  Mean scores  Response  Reversible (days)
 1  Erythema (redness) and eschar formation  0  0  0  0.0  -  1*
   Oedema formation  0  0  0  0.0  -  na
 2  Erythema (redness) and eschar formation  0  0  0  0.0  -  na
   Oedema formation  0  0  0 0.0  -  na
 3  Erythema (redness) and eschar formation  0  0  0  0.0  -  1
   Oedema formation  0  0  0  0.0  -  na

no positive response : mean scores <2 = -

positive response : mean scores , >2 = +

na: not applicable

* : in respect of the result 1 h post application

Interpretation of results:
GHS criteria not met
Executive summary:

The irritant / corrosive potential of the test substance was studied on the skin of rabbits. The method used complied with the OECD - Guideline for Testing of Chemicals No. 404 -" Acute Dermal Irritation/Corrosion"; adopted: 24th April 2002 and the EEC Directive No. 440/2008 Part B - Method BA. According to classification criteria the test substance is not an irritant to the skin. There were 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
For reasons of animal welfare a sequential testing strategy was followed in accordance with the current version of the EEC Directive No. 440/2008 and the OECD Guideline No. 405, irrespective of the requirements of other guidelines for testing for eye irritation/corrosion in rabbits.
This testing strategy comprised a stepwise approach including the evaluation of existing human and/or animal data showing effects on the eye or the skin, the performance of a SAR evaluation for eye and skin corrosion/irritation, measurement of pH value, the evaluation of data on systemic toxicity via the dermal route, the performance of a validated in vitro test for skin corrosion (T 3081239, not corrosive), an in vitro test for skin irritation (T 2081238, not irritating) and an in vitro HET-CAM test for mucosal irritation hazard before in vivo testing for eye irritation/corrosion in rabbits.
The in vitro HET-CAM test is archived under T 5081240. The test compound is not irritating.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: The other eye, which remained untreated, served as control.
Duration of treatment / exposure:
0.1 g of the pulverized test substance was placed into the conjunctival sac of one eye of the first animal after having gently pulled the lower lid away from the eyeball. The lids were gently held together for about one second in order to prevent loss of the test compound. The other eye, which remained untreated, served as control. The treated eye was rinsed 1 hour following instillation.
Because of the fact that one hour after treatment a severe irritation was observed in the first animal, only one further rabbit was treated as described.
Observation period (in vivo):
Eye irritations were scored and recorded approximately at 1, 24, 48 and 72 hours post application (in the following p.a.). If no irritation indices were observed after 72 h, the study was finished. If eye irritations were 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:
Two animals were used for the study.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.5
Max. score:
2
Reversibility:
fully reversible within: 3d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7d

Summary of Irritant Effects (Score)

Animal   Effect  24 h  48 h  72 h  Mean scores  Response  reversible (days)
 1  corneal opacity  4  3  3  3.3  ++  14
   iritis  *  1  0  0.5  -  3
   redness conjunctivae  2  3  3  2.7  +  7
   chemosis conjunctivae  2  2  2  2.0  +  7
 2   corneal opacity  2  2  2  2.0  +  7
   iritis  1  1  1  1.0  +  7
    redness conjunctivae  2  2  2  2.0  -  7
   chemosis conjunctivae  3  2  1  2.0  +  7

response:

corneal opacity: mean scores < 2 = -, = 2 < 3 = +, = 3 = ++

iritis: mean scores < 1 = -, = 1 < 2 = +, = 2 = ++

conjunctival redness: mean scores < 2.5 = -, = 2.5 = +

conjunctival oedema : mean scores < 2 = -, = 2 = +

* Iris not observable, therefore not to investigate.

Interpretation of results:
GHS criteria not met
Executive summary:

The irritant / corrosive effects of the test substance were tested on the eye of female New Zealand White rabbits. The method used complied with the OECD - Guideline for Testing of Chemicals No. 405 -"Acute Eye Irritation/Corrosion"; adopted: 24th April 2002 and EEC Directive No. 440/2008 Part B - Method B.5. According to classification criteria the test substance causes serious damage to eyes with full reversibility within 14 days. There were no systemic intolerance reactions.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

A study for predicting non-specific, corrosive potentials of compounds by using reconstructed human skin was performed. The experiment was carried out on a reconstructed human epidermis EST-1000 (CellSystems, ST. Katharinen, Germany) for detection of topically applied skin corrosives with the test item. Corrosive skin effects of substances are defined as irreversible damage of skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test substance for up to 4 hours. A 100% concentration was tested on the skin/ epidermal equivalents in triplicate. For the determination of time related cytotoxic effects the incubation periods were 3 min. and 60 min. respectively. Thus the study was conducted in accordance with the 431 guideline as well as with an EC guideline (amending Council Directive 67/548/EEC, B.40 Skin Corrosion) using the test item concentrations and incubation periods recommended there. These tests are also related to the revised OECD 404 guideline "Acute Dermal Irritation/Corrosion". To check the reliability of this test procedure a blinded positive/negative control study is conducted at regular interval in the lab. The reliability check is always performed by two technicians, in two laboratories in parallel using the same batches of the control test items.

The test item was applied at a 100% concentration, i.e. 25 mg per insert (plus 50µl 0.9% NaCl to moisten and ensure good contact with the skin).

The test result shows that no corrosive property of the test item was determined by the assay used (Wingenroth, 2010).

Another study which allows the hazard identification of irritant substances in accordance with UN GHS category 2, was performed. The experiment was carried out according to EU Test Method B.46 using commercially available reconstructed human epidermis (RHS) model EST-1000 (CellSystems, St.Katharinen, Germany). Undiluted test substance was applied topically to the RHS model, i.e. 30 mg per insert (plus 30 µg 0.9% NaCI to moisten and ensure good contact with the skin; three replicates). After an exposure period of 20 minutes, followed by a 42 hours post treatment incubation period, the cell viability was measured to be 99.56% in the MIT (Methylthiazoletetrazolium) conversion assay. The results of the concurrent negative control (NC, 0.9% NaCI) and positive control (PC, 5% SOS) demonstrated the viability (NC) and sensitivity (PC) of the test model. Thus, the results show that the test substance is considered to have no skin irritation category (Wingenroth, 2010).

The irritant / corrosive potential of the test substance was studied on the skin of rabbits. The method used complied with the OECD - Guideline for Testing of Chemicals No. 404 -" Acute Dermal Irritation/Corrosion"; adopted: 24th April 2002 and the EEC Directive No. 440/2008 Part B - Method BA. According to classification criteria the test substance is not an irritant to the skin. There were no systemic intolerance reactions (Gmelin, 2010).

Hen's egg tests are used to determine the potential irritant/ corrosive property of a test compound using an in vitra alternative to the Draize methodology (OECD405). The test substance was tested by observing possible adverse changes after application onto the Chorioallantoic membrane (HET-CAM). After the application of the test item blood vessels and albumin were examined and scored for the following irritant effects: vasodilatation, slight hemorrhage; vessel lysis, strong hemorrhage; blood coagulation, albumen coagulation for a period of 300 seconds. 300 µl of the test item was applied per egg directly on the Chorioallantoic membrane. The test substance was identified as "non irritant" to the Chorioallantoic membrane (Irritation Score (IS) = O) under the conditions of this assay.

The irritant / corrosive effects of the test substance were tested on the eye of female New Zealand White rabbits. The method used complied with the OECD - Guideline for Testing of Chemicals No. 405 -"Acute Eye Irritation/Corrosion"; adopted: 24th April 2002 and EEC Directive No. 440/2008 Part B - Method B.5. According to classification criteria the test substance causes serious damage to eyes with full reversibility within 14 days. There were no systemic intolerance reactions (Gmelin, 2010 DRAFT).

Justification for classification or non-classification

According to the available test results and respective classification criteria the test substance is not an irritant to the skin and needs no classification as an skin irritant or as skin corrosive.

The Compound is labeled with R41 (risk of serious damage to eyes); according to REACH TGD ´Guidance on information requirements and chemical safety assessment, Part E: Risk Characterization, May 2008´ this translates to the “moderate hazard band”.