Registration Dossier

Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-09-01 until 1987-09-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: 99.5%
- Storage condition of test material: dry under inert gas

Test animals

Species:
rabbit
Strain:
other: Small Russian
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach, Germany
- Weight at study initiation: 2.4 - 2.5 kg
- Housing: singly in stainless steel cages
- Diet: rabbit diet K4, Ssniff Spezialfutter GmbH, Soest, germany, ad libitum
- Water tap water ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-
- Humidity (%): 60 +/-5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12



IN-LIFE DATES: From: 1987-09-01 To: 1987-09-15

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 500 µL
Duration of treatment / exposure:
4 hrs
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: the application site was covered with a gauze patch (2.5 x 2.5 cm) followed by an impervious polyethylene foil. The patch was help in place by a flexible cotton wrap.


REMOVAL OF TEST SUBSTANCE
- Washing: yes, with water
- Time after start of exposure: 4 hrs


SCORING SYSTEM: according to OECD 404 test guideline

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hrs
Score:
6.75
Max. score:
8
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
4
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
4
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
4
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 h
Score:
4
Max. score:
4

Any other information on results incl. tables

Individual test results were as tabulated below. In addition, the skin was coloured in all animals at 24 hrs (yellow) and at 48 hrs (brown).

Animal

No.

1 h

24 h

48 h

72 h

6 d

8 d

10 d

14 d

ery

ede

ery

ede

ery

ede

ery

ede

ery

ede

ery

ede

ery

ede

ery

ede

1

2

3

3

4

3

4

4

4

scab

Scab, des

des, scar

scar

2

2

3

3

4

3

4

4

4

scab

scab, rup

scab, rup

scab, des, scar

3

2

3

3

4

3

4

4

4

scab, rup

scab, rup

scab, rup

scab, des, scar

Abbreviations:

Ery: erythema; ede: edema; figures: scores according to OECD 404

scab: scab formation; rup: ruptured; des: desquamation; scar: scar formation

No necrosis of the epidermis was reported.

A mean irritation index of 6.75 (maximum possible: 8) was calculated as the sum of all erythema and edema scores of all animals at 1, 24, 48, and 72 hours after patch removal, divided the number of animals (3) and time points (4).

The evaluation according to the directive 79/831/EEC gave means for each animal of 3.33 (erythema) and 4.0 (edema).

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
2-EH was highly irritating, as severe irreversible skin reactions were noted in all treated animals during 24 through 72 hours after patch removal which developed into formation of new skin and scars within 2 weeks after patch removal.

Executive summary:

The skin irritation potential of 2 -EH, purity 99.5%, was tested in a valid non-GLP OECD 404 study using 3 rabbits. Severe erythema and edema was noted in all treated animals at 24 hours after treatment which persisted until 72 hours. The skin reactions caused irreversible changes and resulted in scab formation, desquamation, formation of new skin in all animals during days 6 through 14 after patch removal. Scars and peeling scabs were observed on day 14 in all animals. The observed effects including the late scarification are consistent with a strong irritant, but not a corrosive agent.

2 -EH was irritating according to EU legislation (Council directive 67/548/EEC and its amendment 79/831/EEC),

requiring the label Xi and R38 (Hüls AG, 1987). With respect to the CLP regulation (Regulation (EC) no 1272/2008) a classification in Skin Irritation category 2 seems justified.