Registration Dossier

Administrative data

Description of key information

- skin: rabbit, occlusive 4 h: not irritating (89-0638-FGT)
- eye: rabbit, 0.1 mL: not irritating (2001-0120-DGT)

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:
April 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
yes
Remarks:
occlusive coverage; no further observations after 72 h to establish reversibility
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harald Schriever, Kaninchenfarm, Bremervörde, Germany
- Weight at study initiation: 2.4 - 2.8 kg
- Housing: individually (cages: 40 cm x 45 cm x 50 cm)
- Diet: ad libitum
- Water: ad libitum tap water; analysed regularly
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 2
- Humidity (%): 50 -85
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: March, 21th 1989 To:
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: skin areas without test substance
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL is directly applied to skin
- Concentration (if solution): undiluted (pH 6.5)
Duration of treatment / exposure:
4 hours
Observation period:
30 - 60 min, 24 h, 48 h and 72 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: left scarified and shaved dorsal area and right shaved (but not scarified) dorsal area of the trunk; the sacrified area was not taken into account for assessment of skin irritation potential
- % coverage: 2.5 x 2.5 cm
- Type of wrap if used: "Kosmoplast" and "Elastoplast" (breathable) patches and additional wrapping of the trunk with "Stülpa"

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with tepid water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to guideline (Draize scores)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: average over 24 h/48 h/72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: average over 24 h/48 h/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: average over 24 h/48 h/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: average over 24 h/48 h/72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: average over 24 h/48 h/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: average over 24 h/48 h/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: average over 24 h/48 h/72 h
Score:
1.67
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: average over 24 h/48 h/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: average over 24 h/48 h/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: average over 24 h/48 h/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: average over 24 h/48 h/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: average over 24 h/48 h/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable

Erythema formation scores (max. score 4) for each animal at the time points 24, 48 and 72 hours after patch removal

Animal No.

24 hours

48 hours

72 hours

Mean value from gradings at 24, 48 and 72 hours

test substance

control

test substance

control

test substance

control

Test substance

1

2

0

2

0

1

0

1.67

2

1

0

1

0

1

0

1

3

1

0

1

0

0

0

0.67

4

2

0

2

0

1

0

1.67

5

1

0

1

0

0

0

0.67

6

0

0

0

0

0

0

0

Oedema formation scores (max. score 4) for each animal at the time points 24, 48 and 72 hours after patch removal

Animal No.

24 hours

48 hours

72 hours

Mean value from gradings at 24, 48 and 72 hours

test substance

control

test substance

control

test substance

control

Test substance

1

2

0

2

0

1

0

1.67

2

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

4

1

0

1

0

1

0

1

5

0

0

0

0

0

0

0

6

0

0

0

0

0

0

0

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jan. 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 1987-02-24
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Spain S.p.A (Como) and bred by P.O.A.D.A Mandello Lario (CO), Italy
- Age at study initiation: 10 - 13 weeks
- Weight at study initiation: 2.1-2.5 kg
- Housing: individually housing in stainless steel cages (69x45x51cm) with grid floors
- Diet: ad libitum anti-biotic free pelleted laboratory diet (Altromin MSK)
- Water: ad libitum drinking water via water bottles
- Acclimation period: 10 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 +/- 2
- Humidity (%): 55 +/- 15
- Photoperiod (hrs dark / hrs light): 12 / 12



Vehicle:
unchanged (no vehicle)
Controls:
other: left eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100% (w/w)

Duration of treatment / exposure:
single treatment (right eye),
eye not rinsed
Observation period (in vivo):
1, 24, 48, 72 hours and 7 days after treatment
Number of animals or in vitro replicates:
3 females
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: average 24, 48 and 72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: average 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: average 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: average 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: average 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: average 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: average 24, 48 and 72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: average 24, 48 and 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: average 24, 48 and 72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: average 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: average 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: average 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion:

1-chlorobutane was tested for acute dermal irritation/corrosion in a GLP-guideline study similiar to OECD Guideline 404 (1981). 0.5 mL of the test substance was applied occlusive in a single dose to the skin of 6 New Zealand White rabbits for 4 hours. Grading of skin reactions for erythema and oedema formation according to Draize was performed 30 - 60 minutes, 24, 48 and 72 hours after patch removal. The mean value of the scores for either erythema or oedema formation calculated over all the animals tested is 1.0 and 0.4, respectively. There were no further observations after 72 hours to establish the reversibility. However, there are indications, that the effects might be reversible, because in some animals erythema and oedema formations relieve within 72 hours. In the remaining animals, there were clear signs for recovery, expressed as decreasing scores with proceeding time. Additionally, when considering the occlusive skin treatment, which will cause more severe effects than semi-occlusive treatment, and the trend to reversibility of the effects at study termination after 72 hours, reversibility of all skin reactions may be assumed on day 14.

 

Eye irritation:

The acute eye irritation of n-butyl chloride was investigated in a GLP-guideline study (EU-method B.5) in the rabbit. A 0.1 mL aliquot of 1-chlorobutane was introduced in the right eye of a total of 3 female New Zealand White strain rabbits (no washout). The left eye, which remarks untreated, served as control. The resulting reaction to the substance was examined 1, 24, 48, 72 hours and 7 days after treatment. Slight discharge, a slight to well-defined chemosis and redness was noted in the 3 rabbits at the 1 hour examination. One animal showed a slight discharge, a well-defined redness and a moderate chemosis 24 and 48 hours after treatment. A slight redness was seen in a second animal at these examination times, while recovery had been observed in the third animal 24 hours after dosing. A slight redness and chemosis were still present in 2 rabbits 72 hours after dosing. Complete recovery has occured by day 7. Systemic toxic effects could not be detected and the body weight development of the test animals were not affected.

Justification for classification or non-classification

The data is conclusive but not sufficient for classification according to DSD (67/548/EEC) and CLP (1272/2008/EC).