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Description of key information

In a skin irritation study similar to OECD TG 404, the test substance was found to be non-irritating to the shaved skin of rabbits after 4 hours exposure under semi-occlusive conditions. In an older study performed under occlusive conditions of unchanged test substance a corrosive potential was observed after 1 hour exposure.


The substance is irritative to eyes when tested in rabbits.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
The sudy was conducted according to Draize: Appraisal of the safety of chemicals in foods, drugs and cosmetics. In dermal toxicity pp. 46 - 59, 1959. Austin, Tex.: Association of food and drug officials of the United Staates, Texas, State Department of Health.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gaukler, Germany
- Age at study initiation: no data
- Weight at study initiation: 3.1 resp. 3.02 kg
- Housing: single, cage made of stainless steel with wire mesh walk floor, floor area about 40 cm x 51 cm
- Diet: ca. 130 g daily per animal, Ovator Sokikanin 4 mm, Duesseldorf, Germany
- Water: ca. 250 mL daily per animal, VE water/tap water
- Acclimation period: About 8 days before the beginning of the study in the laboratory, same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: ca. 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: : 2.5 x 2.5 cm (back or flank)
- Type of wrap: breathable bandage

REMOVAL OF TEST SUBSTANCE
- Washing: no

OBSERVATION TIME POINTS
15 - 30 minutes after removal of the test patches and 24 h, 48 h, 8 d after beginning of application

SCORING SYSTEM:
- Method of calculation: Draize
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Remarks:
No results for 72 h are available.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline available
Principles of method if other than guideline:
Test material was administered to the eyes of 4 rabbits to investigate irritative properties.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
other: Undiluted and 1% in propylene glycol
Controls:
no
Amount / concentration applied:
Administered undiluted and as 1% in propylene glycol.
Duration of treatment / exposure:
No data
Observation period (in vivo):
No data
Number of animals or in vitro replicates:
4 rabbits
Details on study design:
Undiluted test material was administered to the eye of a rabbit and left unwashed. Undiliuted test material was also administered to the eye of a rabbit and then the eye was washed with water.

The test material was administered as 1% in propylene glycol to the eye of a rabbit and left unwashed. The 1% in propylene glycol was also administered to the eye of a rabbit and then the eye was washed with water.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
overall irritation score
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Undiluted test material- unwashed: moderate conjunctivitis and corneal necrosis
Undiliuted test material- washed: slight conjunctivitis and corneal necrosis

1% in propylene glycol- unwashed: slight pain and questionable irritation
1% in propylene glycol- washed: no significant response

Butylene Oxide is moderately irritating to the eyes. Undiluted butylene oxide presents a definite hazard of eye injury. Pain and conjunctival inflammation may persist for several days. Transient corneal injury may occur, but is expected to heal completely within a few days. Weak solutions (1% or less) are not irritating to the eye.

Interpretation of results:
study cannot be used for classification
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline available
Principles of method if other than guideline:
Range finding tests
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.005 mL or 0.02 mL
Duration of treatment / exposure:
no data
Observation period (in vivo):
no data
Number of animals or in vitro replicates:
no data
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
overall irritation score
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Instillation of 0.005 mL in rabbit eyes caused moderate corneal damage, and 0.02 mL caused marked damage. Irritation grade= 5.
Interpretation of results:
study cannot be used for classification
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline followed
Principles of method if other than guideline:
Study according to BASF-internal standards.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: female 2.7 kg, male 2.71 kg
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent negative control
Amount / concentration applied:
0.05 mL
Duration of treatment / exposure:
20 hours
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Findings after       
 1 hour  24 hours  8 days
 slight reddening, slight edema, secretion  slight reddening, edema and cloudiness, smeary stratification  no findings

NaCl solution showed no eye irritation.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation/corrosion


In a skin irritation test according to the method of Draize, the test substance was found to be non-irritating on rabbit skin after 4 hours exposure (BASF, 1981). The test substance was administered unchanged under semi-occlusive conditions to the shaved skin.


In another skin irritation test following BASF-internal guidelines (BASF,1979) the substance was found to possess a corrosive potential after 1 hour exposure under occlusive conditions (unchanged test substance).


In a further study skin irritation was found after 20-hour exposure to rabbits under occlusive conditions. The unchanged test substance was applied (BASF, 1979).


Dow (1965) reported no skin irritation when administered the undiluted test material to the intact and abraded skin of rabbits. It was concluded, that prolonged contact might burn the abraded skin.


No skin irritation was found for rabbits when administered undiluted test substance to the clipped skin and uncovered under open conditions (Dow, 1958).


In an older study (Dow, 1953) it was concluded that the test substance is severely irritating to the skin of rabbits upon prolonged exposure. A single prolonged contact with the undiluted test substance caused blistering and necrosis. Prolonged and repeated contact with solutions of the order of 1% caused severe irritation and superficial necrosis. A single short exposure should cause no reactions.


Based on the whole information available it was concluded that the substance is irritating to the skin.


Eye irritation


For this endpoint a WoE approach was applied.


A study was performed in rabbits. The test substance was given unchanged into the right eye for 20 hours. For comparison, NaCl solution was given in the left eye. After 24 h, slight redding, edema and cloudiness was observed in the treated eye. This was fully reversible after 8 days. The negative control showed no eye irritation (BASF 1975).


In a further study undiluted test material was administered to the eye of a rabbit and left unwashed.  Undiluted test material was also administered to the eye of a rabbit and then the eye was washed with water. Furthermore, the test material was administered as 1% in propylene glycol to the eye of a rabbit and left unwashed. The 1% in propylene glycol was also administered to the eye of a rabbit and then the eye was washed with water. Butylene Oxide is moderately irritating to the eyes. Undiluted butylene oxide presents a definite hazard of eye injury. Pain and conjunctival inflammation may persist for several days. Transient corneal injury may occur, but is expected to heal completely within a few days. Weak solutions (1% or less) are not irritating to the eye (Dow, 1953).


In another study, the unchanged test substance was administered to rabbits eyes (0.005 mL or 0.02 mL). Instillation of 0.005 mL in rabbit eyes caused moderate corneal damage, and 0.02 mL caused marked damage (Dow, 1958).


Based on the study data it was concluded that the substance is irritating to eye.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008


The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data the substance is classified for skin irritation Cat.2 (H315) and eye irritation Cat. 2 (H319) according to Regulation (EC) No 1272/2008 (CLP). The substance is harmonized classified for skin irritation Cat.2 (H315) and eye irritation Cat. 2 (H319) according to Annex VI of Regulation (EC) No 1272/2008. Furthermore, the substance is harmonized classified for STOT SE 3 (H335) according to Annex VI of Regulation (EC) No 1272/2008.