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Administrative data

Description of key information

Skin irritation (in vivo): Corrosion (OECD 404)

The skin irritation /corrosion study identified as key study was performed according to OECD 404 and under GLP. The C12-18-alkylbis(hydroxyethyl)methyl, chloride (77% in isopropyl alcohol)  was given as a single dermal application to one female New Zealand White albino rabbit at a dose of 0.5 g. The examination of the test site immediately after the patch removal revealed erythema grade 1 and oedema grade 1 for the 3 min exposure, erythema grade 1 and oedema grade 2 for the 1 hour exposure and erythema grade 2 and oedema grade 3 for the 4 hour exposure.

The evaluation of the grades for 3 min exposure showed irritation, and 1 hour and 4 hours showed corrosive effects which were not fully reversible within the observation period. Based on these results and according to Annex I of Regulation (EC) 1272/2008, the test item C12-18-alkylbis(hydroxyethyl)methyl, chloride (77% in isopropyl alcohol) has obligatory labelling requirement for skin irritation and has to be classified into Category 1 B.

Eye irritation (in vivo): irreversible effects to the eye

No key study was selected since the two available studies on eye irritation are of low quality with limited information on the testing procedure. Based on animal welfare grounds, it is not considered justified to perform any additional testing for this endpoint.

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
Study period:
2011-11-14 to 2011-11-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Semi barrier in an air-conditioned room
- Temperature: 18 +/- 3 °C (recommendations of TVT, GV-SOLAS)
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: at least 10 x / hour
- Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 0700), rich in crude fibre
- Free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Housed in ABS - plastic rabbit cages, floor 4200 cm2
- Adequate acclimatisation period (at least 5 days) under laboratory conditions

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
As the test item was suspected to be corrosive, three patches were applied to one animal. The exposure periods were 3 min, 1 hour and 4 hours.
At the end of the exposure period, the residual test item was removed with tap water.
Observation period:
14 days after the patch removal
Number of animals:
1
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 3 min exposure - 24h to 48h
Score:
2
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 3 min exposure - 24h to 72h
Score:
1
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1h exposure - 24h to 72h
Score:
3
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1h exposure 24h to 72h
Score:
2
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 4h exposure - 24h to 72h
Score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 4h exposure - 24h to 72h
Score:
2
Irritant / corrosive response data:
Initial test in animal no. 1: The examination of the test site immediately after the patch removal revealed erythema grade 1 and oedema grade 1 for the 3 min exposure, erythema grade 1 and oedema grade 2 for the 1 hour exposure and erythema grade 2 and oedema grade 3 for the 4 hour exposure.
The subsequent clinical observations showed irritant effects for the 3 min exposure and corrosive effects for the 1 hour and 4 hours exposure, which were not reversible within the observation period of 14 days.
Irritant effects were observed on the intact skin of one female rabbit (strain NZW) after a contact time of 3 min (Tables), corrosive effects were observed on the intact skin of one female rabbit after a contact time of 1 hour and 4 hours. These signs of irritation / corrosion were not reversible within the observation period of 14 days.

Dermal Irritation Evaluation

Exposure Time

Application
Site

Irritation (hours after patch removal)

1 hour

24 hours

48 hours

72 hours

T

C

T

C

T

C

T

C

3 min

Erythema

1

0

2

0

2

0

2

0

Oedema

1

0

1

0

1

0

1

0

1 hour

Erythema

1

0

3

0

3

0

3

0

Oedema

2

0

2

0

2

0

2

0

4 hours

Erythema

3

0

4

0

4

0

4

0

Oedema

3

0

2

0

2

0

2

0

Exposure Time

Application
Site

Irritation (days after patch removal)

4 days

5 days

6 days

7 days

T

C

T

C

T

C

T

C

3 min

Erythema

2

0

2

0

2

0

1

0

Oedema

1

0

1

0

0

0

0

0

1 hour

Erythema

3

0

3

0

3

0

2

0

Oedema

2

0

2

0

0

0

0

0

4 hours

Erythema

4

0

4

0

4

0

4

0

Oedema

2

0

2

0

0

0

0

0

Exposure Time

Application
Site

Irritation (days after patch removal)

8 days

9 days

10 days

11 days

T

C

T

C

T

C

T

C

3 min

Erythema

1

0

1

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

1 hour

Erythema

2

0

2

0

1

0

1

0

Oedema

0

0

0

0

0

0

0

0

4 hours

Erythema

4

0

4

0

4

0

3

0

Oedema

0

0

0

0

0

0

0

0

Exposure Time

Application
Site

Irritation (days after patch removal)

12 days

13 days

14 days

 

T

C

T

C

T

C

 

3 min

Erythema

1

0

1

0

0

0

 

Oedema

0

0

0

0

0

0

 

1 hour

Erythema

2

0

2

0

1

0

 

Oedema

0

0

0

0

0

0

 

4 hours

Erythema

4

0

4

0

4

0

 

Oedema

0

0

0

0

0

0

 

Other findings:

Individual Systemic and Local Findings – 3 min exposure

Time after
Patch Removal

Systemic Findings

Specific Local Findings (apart from erythema/oedema)

Comments

1 hour

nsf

nsf

-

24 hours

nsf

nsf

-

48 hours

nsf

nsf

-

72 hours

nsf

nsf

-

4 days

nsf

eschar, superficial cleft

-

5 days

nsf

eschar, superficial cleft

-

6 days

nsf

eschar, superficial cleft

-

7 days

nsf

eschar, desquamation

-

8 days

nsf

eschar, desquamation

-

9 days

nsf

eschar, desquamation

-

10 days

nsf

eschar, desquamation

-

11 days

nsf

eschar, desquamation

-

12 days

nsf

eschar, desquamation

-

13 days

nsf

dequamation

-

14 days

nsf

dequamation

-

Individual Systemic and Local Findings – 1 hour exposure

Time after
Patch Removal

Systemic Findings

Specific Local Findings (apart from erythema/oedema)

Comments

1 hour

nsf

nsf

-

24 hours

nsf

eschar

-

48 hours

nsf

eschar

-

72 hours

nsf

eschar

-

4 days

nsf

eschar, cleft

-

5 days

nsf

eschar, cleft

-

6 days

nsf

eschar, cleft

-

7 days

nsf

eschar, desquamation

-

8 days

nsf

eschar, desquamation

-

9 days

nsf

eschar, desquamation

-

10 days

nsf

eschar, desquamation

-

11 days

nsf

eschar, desquamation

-

12 days

nsf

eschar, desquamation

-

13 days

nsf

eschar, desquamation

-

14 days

nsf

eschar, desquamation

-

Individual Systemic and Local Findings – 4 hours exposure

Time after
Patch Removal

Systemic Findings

Specific Local Findings (apart from erythema/oedema)

Comments

1 hour

nsf

nsf

-

24 hours

nsf

eschar

-

48 hours

nsf

eschar

-

72 hours

nsf

eschar

-

4 days

nsf

eschar

-

5 days

nsf

eschar

-

6 days

nsf

eschar

-

7 days

nsf

eschar

-

8 days

nsf

eschar

-

9 days

nsf

eschar

-

10 days

nsf

eschar

-

11 days

nsf

eschar

-

12 days

nsf

eschar

-

13 days

nsf

eschar

-

14 days

nsf

eschar

-

Body Weight Develompent:

 

Animal No. 1

Start of Study
(weight in kg)

2.5

72 Hours after Application (weight in kg)

2.4

End of Study
(weight in kg)

2.7

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of the present study, the single dermal application of the test item C12-18-alkylbis(hydroxyethyl)methyl, chloride (77% in isopropyl alcohol) to one rabbit at a dose of 0.5 g for 3 min exposure showed irritant, for 1 hour and 4 hours exposure showed corrosive effects which were not fully reversible within the observation period.
Neither mortalities nor significant clinical signs of toxicity were observed.
In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001/59/EC, the test item C12-18-alkylbis(hydroxyethyl)methyl, chloride (77% in isopropyl alcohol) has obligatory labelling requirement for skin irritation with R34.
According to Annex I of Regulation (EC) 1272/2008, the test item C12-18-alkylbis(hydroxyethyl)methyl, chloride (77% in isopropyl alcohol) has obligatory labelling requirement for skin irritation and has to be classified into Category 1 B.
According to GHS (Globally Harmonized Classification System), the test item C12-18-alkylbis(hydroxyethyl)methyl, chloride (77% in isopropyl alcohol) has obligatory labelling requirement for skin irritation and is classified into Category 1 B.
Executive summary:

On the basis of the test results given below and in conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC, the substance should be assigned the following risk phrase:

R38 irritating to skin

 

 

 

R34 causes burns

X

 

 

R35 causes severe burns

 

 

 

no phrase

 

On the basis of the test results given below and in conformity with the criteria given inAnnex I of Regulation (EC) 1272/2008, the substance should be:

classified into category 1 A

 

 

classified into category 1 B

X

 

classified into category 1 C

 

 

 

classified into category 2

 

 

 

not classified

 

On the basis of the test results given below and in conformity with the criteria given inGHS (Globally Harmonized System of Classification and Labelling of Chemicals), the substance should be:

classified into category 1 A

 

 

classified into category 1 B

X

 

classified into category 1 C

 

 

 

classified into category 2

 

 

 

classified into category 3

 

 

 

not classified

 

Species/strain:                        New Zealand White Rabbits Crl: KBL (NZW)

Number of animals:               1

Duration of exposure:           3 min, 1 hour, 4 hours

Amount of substance:           0.5 mL per test site

Type of dressing:                   occlusive  [    ]  semi-occlusive  [ X ]

First time of effects:             3 min exposure: directly after patch removal erythema grade 1, oedema grade 1

1 hour exposure: directly after patch removal erythema grade 1, oedema grade 2

4 hour exposure: directly after patch removal erythema grade 2, oedema grade 3

Last time of effects:             3 min exposure: 14 days after patch removal desquamation

1 hour exposure: 14 days after patch removal erythema grade 1, desquamation, eschar

4 hour exposure: 14 days after patch removal erythema grade 2, eschar

Reversibility of the

observed effects:                  the changes were not fully reversible within the observation period

Method:                                OECD 404
EC 440/2008, Method B.4
OPPTS 870.2500

Average Scores – (24, 48, 72 hour reading)

Exposure

Mean 24 – 72 hours

Erythema

Oedema

3 min

2

1

1 hour

3

2

4 hours

4

2

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin
Three skin irritation studies of different quality are availableon C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2). The key study is performedaccording to OECD 404 and under GLP conditions. In this study 0.5 g of the test material was applied to the intact skin of one female New Zealand White albino rabbit. The subsequent clinical observations after the exposure for 3 min showed irritation, and exposure for 1 hour and 4 hours showed corrosive effects which were not fully reversible within the observation period. The result is consistent with an older, less compliant, study (Kukulinsky, 1979) where the test substance was not so clearly specified and the results from the Kukulinsky study could not be used for classification in accordance with modern regulations.

 

The in vitro skin irritation study reported gives no indications on corrosive properties when tested in the EpiDerm human skin model. For several other amine-based substances, it has been seen that in vitro tests significantly underestimate the skin irritation potential. This was also seen for this particular substance, which was negative in an in vitro test, and showed corrosive effects in the key study in vivo test (Lütkenhaus, 2011).


Eye 

Two in vivo eye irritation studies are available onC12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2), but no study was selected as key study, since the two studies are of low quality with limited information on the testing procedure. Based on animal welfare grounds, it is not considered justified to perform any additional testing for this endpoint.

 

Both the available eye irritation studies indicate GHS Cat 1 for eye irritation, which is further supported by the corrosive nature of the substance to skin.In the eye irritation study with the highest validity rating (Kay, 1959) one albino New Zealand White rabbit per concentration was administered a single ocular dose of 0.1 ml of the diluted test substance (1% or 5%) and observed up to eight days after instillation.The test result from the study with the 5% solution indicates a classification as an eye irritant Category 1 is needed with Symbol "Corrosion"; Signal word "Danger"; Hazard statement 318: "Causes serious eye damage". This is further supported by the test result from the other eye irritation study, with validity rating 3, and the corrosive nature of the substance to skin.

Justification for selection of skin irritation / corrosion endpoint:

The chosen study is a Klimisch 1 GLP study performed on C12-18-alkylbis(hydroxyethyl)methyl, chloride, CAS no 71808-53-2, according to current guidelines.

Justification for selection of eye irritation endpoint:

No key study was selected since the two available studies on eye irritation are of low quality with limited information on the testing procedure.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin

The conclusion from the three available studies is that the substanceC12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) has to be classified for skin irritation as Category 1 B according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008.

 

Eye

Both the available eye irritation studies indicateGHS Cat 1 for eye irritation, which is further supported by the corrosive nature of the substance to skin.The conclusion from the studies available is that the substanceC12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) has to beclassified as an eye irritant Category 1 under GHS: Symbol "Corrosion"; Signal word "Danger"; Hazard statement 318: "Causes serious eye damage"according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008.