Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The report in a compilation of data from studies conducted between 1958 and 1972. The data obtained from these studies are believed to be reliable despite of the fact, that the studies do not follow today's guideline requirements and that the test substance was not defined in terms of purity.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Principles of method if other than guideline:
The original study was conducted in 1972 according to the Draize Test; the assessment of the findings followed the FDA method(Federal Register, 37, No.83, 191.12, 1972). GLP was not compulsory at the time the studies were performed.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
No purity given.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Sex: female
Age/weight at study initiation: No data.

Test system

Vehicle:
other: PEG400
Controls:
yes, concurrent vehicle
Amount / concentration applied:
study TXM72065: Concentration: 0.5%, 2%, 5%; Amount applied: one drop
Duration of treatment / exposure:
study TXM72065: Treatment once/exposure 24 h
Observation period (in vivo):
study TXM72065: 21 days
Number of animals or in vitro replicates:
study TXM72065: 3 animals per group.
Details on study design:
TXM72065:
New Zealand White female rabbits were used for testing; each test group comprised 3 animals. Bronopol was tested as 0.5%, 2% and 5% solution in PEG 400; PEG 400 was tested in the control group. Each animal received a drop of test solution into the conjunctival sac of one eye; the second eye remained untreated and served as control. After 24 hours, the eyes were rinsed. The first reading of the eyes was performed after 1 hour; further reading time points were: 24 h, 48 h, 72 h, 7 d, 14 d and 21 d following treatment. Examination of the cornea at the time points 24 h, 72 h and 7 d was facilitated by instillation of one drop of fluorescein eye drop into the eye; the excess was flushed away with warm water. The assessment of the findings was based on the F.D.A method (Federal Register, 37, No. 83, 191.12, 1972).

Results and discussion

In vivo

Irritant / corrosive response data:
Study TXM72065, which was conducted 1972.This study was conducted according to Draize (i.e Draize test) and the assessment of the findings followed the F.D.A. method (Federal Register, 37, No. 83, 191.12, 1972). Following findings were reported:
Control (PEG 400) animals: At time point 1 hour, two control animals showed slight redness of the conjunctiva whereas slight to increased discharge was seen in all 3 control-animals. These effects disappeared within 24 hours. No chemosis was seen.
0.5% bronopol-treated animals: At time point 1 hour, all 3 animals showed slight redness of the conjunctiva; one of them also showed slight discharge; all these effect disappeared within 24 hours. No chemosis was seen.
2% bronopol-treated animals: At time point 1 hour, all 3 animals showed slight redness of the conjunctiva; this effect still was seen after 24 hours and in two cases, redness of the conjunctiva still was evident at time point 7 days following treatment. At time point 1 hour, all animals showed moderate to increased eye discharge; however, this effect disappeared within 24 hours. One case of chemosis was reported at time point 1 hour only.
5% bronopol-treated animals: Moderate redness of the conjunctiva was reported for all 3 animals at time point 1 hour; the redness lasted in all 3 animals up to time point 48 h. At time point 72 h, slight to moderate redness still was seen in 2 animals and after 7 days, in one of them. At time point 1 hour, all animals showed moderate to increased eye discharge; this effect lasted in all animals until time point 24 hours, but disappeared thereafter. Moderate to increased chemosis was seen in all 3 animals at time points 1 h and 24 h. At time point 48 h, chemosis remained in one animal; thereafter, no more chemosis was seen. All effects were reversible at least within 7 days. After 14 and 21 days, no more effects were seen. None of the concentrations elicited reactions in the cornea or iris.

Any other information on results incl. tables

Table 0: single animal data (extract from original table) after exposition to 5% bronopol

305 312 309 Mean (24,48,72 h)  
Score Conjunctiva redness 2 2 2 24 h
1 2 2 48 h 
1 2 0 72 h
Mean 1.3 2.0 1.3 1.6  
 
Score Conjunctiva swelling 2 3 2  24 h
0 1 0  48 h
0 1 0  72 h
Mean 0.7 1.7 0.7 1.0  
 
Score Conjunctiva discharge 1 1 2  24 h
0 0 0  48 h
0 0 0  72 h
Mean 0.3 0.3 0.7 0.4  

Table 1: Based on the F.D.A. scoring scale, the results for the different groups can be summarized as follows:

Treatment

Rabbit

Grade of irritation according to FDA scoring method

 

Control (vehicle: PEG 400)

1

negative

 

 2

negative

 3

negative

 0.5% Bronopol  1  negative
   2  negative
   3  negative
 2% Bronopol negative 
   2 negative 
   3 negative 
 5% Bronopol marginal 
   2 strongly irritated 
   3 irritant 

Applicant's summary and conclusion