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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1987-09-01 until 1987-09-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the hazardous degradation product (alcohol) released from the target substance. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance, which might change the hazardous properties of the target substance compared to the properties of the pure alcohol. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across data from the degradation product (relevant alcohol) to evaluate irritation, sensitization and the short term and long-term toxicological effects and mutagenicity of the target substance.

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

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, requiring the label Xi and R38 (Hüls AG, 1987). With respect to the CLP regulation a classification in Skin Irritation category 2 seems justified.