Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
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)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: C12-18-alkylbis(hydroxyethyl)methyl, chloride (77% in isopropyl alcohol)
CAS No.: 71808-53-2 (old CAS No. 70750-47-9)
Chemical Name: C12-18-alkylbis(hydroxyethyl)methyl, chloride
Batch No.: S001314
Physical state at RT: liquid
Colour: amber
Active Components: 77.3%
Storage: at room temperature
Expiry Date: 28.04.2018

Test animals

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

Test system

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

Results and discussion

In vivo

Resultsopen allclose all
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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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