Bis(1-n-butyl-3-methylcyclopentadienyl)zirconium dichloride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source compound [Bis(1,3-dimethylcyclopentadienyl)zirconium dichloride] (CAS No. 119445-92-0) is structurally identical to the target compound [Bis(1-butyl-3-methylcyclopentadienyl)zirconium dichloride] (CAS No. 151840-68-5), with the exception of the presence of a butyl, rather than a methyl group, on the C1 position of both cyclopentadiene rings. Both substances share the same organozirconium structure, comprising of a zirconium central atom, with two cyclopentadienyl rings and two chlorine ligands. Although metabolic data is not available for both substances, they are expected to decompose to identical breakdown products.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Bis(1-butyl-3-methyl cyclopentadienyl)Zirconium dichloride

EC Number:

686-816-3

Cas Number:

151840-68-5

Molecular formula:

C20 H30 CL2 Zr1

IUPAC Name:

Bis(1-butyl-3-methyl cyclopentadienyl)Zirconium dichloride

Test material form:

solid

Test animals / tissue source

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Not specified

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

A single administration of the substance was administered into the conjuctival sac of the left eye. Both eyes were rinsed with water 24 hours after the test substance application.

Observation period (in vivo):

1 hour, 24 hours and 144 hours after instillation. Examination 168 hours after instillation was impossible because of severe inflammation of the eye.

Number of animals or in vitro replicates:

Three (3) rabbits.

Details on study design:

Not specified.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: all three rabbits

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: all three rabbits

Time point:

24 h

Score:

>= 1 - <= 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: all three rabbits

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: all three rabbits

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

chemosis score

Basis:

animal: all three rabbits

Time point:

other: between 1 hour and 168 hours after instillation

Score:

>= 3 - <= 4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Corneal opacity (grade 1) occurred in all three rabbits 1 h after instillation, in grades 1-4 in all three rabbits between 24 h and 144 h after instillation. Because of severe inflammation an evaluation was impossible at the examination 168 h after instillation. The whole cornea was affected at each time-point of examination. From 24 h after dosing onwards the iris of all 3 rabbits did not show any reaction to light, this alteration had not disappeared at study termination. Conjunctival redness (grade 1) occurred 1 h after instillation in all three rabbits, redness increased up to grade 2 between 24 h and 158 h after instillation. Conjunctival chemosis (grades 3-4) was observed between 1 h and 168 h after the instillation in all 3 rabbits. All 3 animals showed conjunctival secretion (grades 1-3) between 1 h and 168 h after the instillation. Secretion was hemorrhagic and purulent after 24 h in all rabbits. The fluorescein test confirm cd corneal changes in form of ulceration and/or necrosis.
Examination after 168 h revealed a very poor general condition of the rabbits as a consequence of the afore-described local changes. Therefore the 3 animals had to be sacrificed at this time-point.

Other effects:

Bodyweight gain and food consumption were within the normal range. The right eye remained untreated and showed no pathological changes.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on the results of this study, Bis (1, 3-dimethylcyclopentadienyl) zirconium dichloride is considered to be severely irritating to the eye.

Executive summary:

In the present examination, the effect of Bis (1, 3-dimethylcyclopentadienyl) zirconium dichloride on the rabbit eye was tested after a single administration into the conjunctival sac. Under the present test conditions, 0.1 g Bis (1, 3-dimethylcyclopentadienyl) zirconium dichloride/eye showed severe adverse effects (both eyes were rinsed with water 24 h after the test substance application). Although the data was not available on an individual animal basis, these data would not have affected the overall severity of the conclusion. Based on the results of this study Bis (1, 3-dimethylcyclopentadienyl) zirconium dichloride is considered to be severely irritating to the eye.