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Administrative data

Description of key information

Skin irritation (rat):  not irritating [Kurth 2006]
Eye irritation (rabbit): not irritating [Amir 2003]

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:
from August 2002 to February 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
- exposure time 24 hrs instead of 4 hrs, 6 animals instead of 3, few details in test description and reporting
GLP compliance:
not specified
Specific details on test material used for the study:
- Solubility and stability of the test substance in the solvent/vehicle: The liquid original compound was used
Species:
rat
Strain:
other: Shoe: WIST (SPF)
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated skin served as control
Amount / concentration applied:
2000 mg/kg bw
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
3 males and 3 females
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.78
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4

Test compound ZK 56406 (2000 gm/kg)

Animal number and sex

Location (finding)

Time-point after end of exposure

20M

21M

22M

4F

5F

6F

Reddening and scab formation

1 hour*

0

0

0

0

0

0

24 or 25 hours

2

2

0

0

0

0

48 hours

2

2

0

0

1

1

72 hours

2

2

0

0

0

0

Individual mean values:

2

2

0

0

0.33

0.33

Mean value of all animals:

0.78

 

Swellings

1 hour*

0

0

0

0

0

0

24 or hours

0

0

0

0

0

0

48 hours

0

0

0

0

0

0

72 hours

0

0

0

0

0

0

Individual mean values:

0

0

0

0

0

0

Mean values of all animals:

0

*         = not included in calculations of mean values

Interpretation of results:
other: very slight local intolerance reactions up to day 6.
Executive summary:

After a single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg very slight local intolerance reactions at the administration area and above were observed up to day 6. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0.

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:
August to September 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
4 animals (2M, 2F)
GLP compliance:
not specified
Specific details on test material used for the study:
- Solubility and stability of the test substance in the solvent/vehicle: The liquid original compound was used
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye, which remained untreated, served as control.
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
test substance remained in the eye (eye was not rinsed)
Observation period (in vivo):
4 days
Number of animals or in vitro replicates:
2 females, 2 males
Details on study design:
0.1 mL corresponded to ca. 91 mg
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
reddening
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
swelling
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.25
Max. score:
4
Reversibility:
fully reversible within: 3 days

Table 1: Results of the study

    

 Irritant effects (score)         

Animal no. (sex)

 Irritation parameter

24 h 48 h  72 h  Mean scores

 1 (M)

 Cornea

0 0.0
 

 Iris

0 0 0 0.0
 

 Conjunctiva (reddening)

0 0 0 0.0
 

 Conjunctiva (swelling)

0 0 0 0.0

 2 (M)

 Cornea

0 0 0 0.0
   Iris 0 0 0 0.0
   Conjunctiva (reddening) 0 0 0 0.0
   Conjunctiva (swelling) 0 0 0 0.0

 3 (F)

 Cornea 0 0 0 0.0
   Iris 0 0 0 0.0
   Conjunctiva (reddening) 1 1 1 1.00
   Conjunctiva (swelling) 1 0 0 0.33
 4 (F)  Cornea  0  0  0  0.0
   Iris  0  0  0  0.0
    Conjunctiva (reddening)  1  1  1  1
    Conjunctiva (swelling)  1  1  0  0.67

The control eyes were without findings.

A single application of 0.1 ml ZK 28520 into the conjunctival sac of the rabbit eye led to slight to moderate secretion, reddening and swelling of the outer eyelids and eyelid closure mainly on days 1-2. Additionally, reddening and swelling of the conjunctivae were observed which were slight to moderate up to day 2, while slight conjunctival reddening and/or vascular injection were observed up to day 7. One animal was without findings on day 2, while the other animals were without findings on days 7 or 8.

Interpretation of results:
other: slight to moderate irritation which is fully reversible on day 7
Executive summary:

In a local tolerance test on the rabbit eye similar to OECD TG 405 a single application of the test substance into the conjunctival sac provoked on the whole slight irritation which lasted up to day 7. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea and iris, 0.25 for conjunctival swelling and 0.50 for conjunctival reddening. According to EU classification criteria the test substance need not be labelled as an eye irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

After a single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg very slight local intolerance reactions at the administration area and above were observed up to day 6. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0.

In a local tolerance test on the rabbit eye similar to OECD TG 405 a single application of the test substance into the conjunctival sac provoked on the whole slight irritation which lasted up to day 7. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea and iris, 0.25 for conjunctival swelling and 0.50 for conjunctival reddening. According to EU classification criteria the test substance need not be labelled as an eye irritant.


Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP) is not required.

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