Registration Dossier

Administrative data

Description of key information

Skin irritation (rabbit): not irritating [Treher 1996a]
Eye irritation (rabbit): not irritating [Treher 1996b]

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:
other information
Study period:
Dec 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
- time-points of evaluation were 20, 44 and 68 hours instead of 24, 48 and 72 hours after end of exposure
GLP compliance:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
physiological saline
Controls:
other: the untreated skin served as control
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
4 days
Number of animals:
2 males and 2 females

The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 20, 44 and 68 hours after the end of administration were 0.

Executive summary:

A single dermal administration of the test substance (0.5 g applied as a paste) for 4 hours to male and female rabbits was tolerated without any local irritations. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 20, 44 and 68 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:
other information
Study period:
Dec 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
- 4 instead of 3 animals
GLP compliance:
yes
Test material information:
Composition 1
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):
7 days
Number of animals or in vitro replicates:
2 males and 2 females
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:
0.1
Max. score:
2
Reversibility:
fully reversible within: 2 days
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: 3 days
Irritation parameter:
conjunctivae score
Remarks:
swelling
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 2 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)

1 0 0 0.3
 

 Conjunctiva (swelling)

0 0 0 0.0

 2 (M)

 Cornea

0 0 0 0.0
   Iris 0 0 0 0.0
   Conjunctiva (reddening) 1 0 0 0.3
   Conjunctiva (swelling) 0 0 0 0.0

 3 (F)

 Cornea 0 0 0 0.0
   Iris 1 0 0 0.3
   Conjunctiva (reddening) 2 1 0 1.0
   Conjunctiva (swelling) 2 0 0 0.7

 4 (F)

 Cornea 0 0 0 0.0
   Iris 0 0 0 0.0
   Conjunctiva (reddening) 1 0 0 0.3
   Conjunctiva (swelling) 0 0 0 0.0

The control eyes were without findings.

The single application of 0.1 ml ZK 9340 (corresponding to 56.1- 62.9 mg) into the conjunctival sac of the right eye led on the application day to slight to moderate secretion, reddening of the outer eyelids and eyelid closure, one animal showing slight swelling of the outer eyelids. Slight to severe reddening and swelling of the conjunctivae was observed in all animals. Additionally, slight to moderate, in one animal severe, vascular injection was observed on the application day. Two animals showed very slight to slight reddening and slight blood vessel injection of the iris on day 1, one animal showed slight reddening of the iris until day 2. On days 2 and 3, very slight to moderate reddening and vascular injection of the conjunctivae was observed in all animals, one animal showed severe vascular injection and one showed slight swelling of the conjunctivae on day 2. These findings gradually faded away, and all animals were without findings 72 hours after application.

Executive summary:

In a local tolerance test on the rabbit eye according to OECD TG 405 a single application of the test substance into the conjunctival sac provoked on the whole moderate irritation on the day of treatment which gradually faded away over several days after application. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameter cornea, 0.1 for iris, 0.2 for conjunctival swelling as well as 0.5 for conjunctival reddening. According to EU classification criteria ZK 9340 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

A single dermal administration of the test substance (0.5 g applied as a paste) according to OECD TG 404 for 4 hours to male and female rabbits was tolerated without any local irritations (Treher, 1996a). The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 20, 44 and 68 hours after the end of administration were 0 according to the system recommended in Directive 67/548/EEC.

In a local tolerance test on the rabbit eye according to OECD TG 405 a single application of the test substance into the conjunctival sac provoked on the whole moderate irritation on the day of treatment which gradually faded away over several days after application (Treher, 1996b). The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameter cornea, 0.1 for iris, 0.2 for conjunctival swelling as well as 0.5 for conjunctival reddening. According to EU classification criteria ZK 9340 need not be labelled as an eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available

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.