Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 March 1994 to 24 March 1994
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Version / remarks:
(1984)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Version / remarks:
(1989)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF 59 NohSan No. 4200 (Guidance on toxicology study data for application of agriculture chemical registration) (1985)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Technical Grade MKH 3586
- Physical state: Beige powder
- Analytical purity: 97.8 - 98.2%
- Purity test date: 17 Jun 1994
- Lot/batch No.: 17004/93
- Expiration date of the lot/batch: 6 months from date of purity testing

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Duration of treatment / exposure:
Single application (unwashed)
Observation period (in vivo):
1, 24, 48, 72 hrs
Number of animals or in vitro replicates:
6 males/dose group

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: All time points
Max. score:
0
Reversibility:
other: No effects observed to the cornea
Irritation parameter:
iris score
Basis:
mean
Time point:
other: All time points
Max. score:
0
Reversibility:
other: No effects observed to the iris
Irritation parameter:
conjunctivae score
Basis:
other: discharge
Time point:
other: 1 hr
Max. score:
2
Reversibility:
fully reversible within: 24 hrs
Irritation parameter:
conjunctivae score
Basis:
other: chemosis
Time point:
other: 1 and 24hrs
Max. score:
1
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Basis:
other: redness
Time point:
other: 1, 24 and 48hrs
Max. score:
1
Reversibility:
fully reversible within: 72 hrs

Any other information on results incl. tables

OBSERVATIONS:

Clinical / eye:

No clinical signs of toxicity or other non-ocular lesions were observed. The cornea and iris showed no lesions or other signs of irritation in any animal. Conjunctival discharge (grade 2) was observed in 3/6 animals 1 hour post dosing and resolved in all of the affected animals by 24 hours post dosing. Chemosis (grade 1) was observed in 6/6 animals 1 hour post dosing. Resolving in 5/6 animals by 24 hours with the final animal returning to normal by 48 hours. Conjunctival redness (grade 1) was observed in 6/6 animals at 1 hour and resolved in 3/6 animals by 48 hours and the other 3/6 by 72 hours (refer to Table 7.3.2).

 

Table 7.3.2: Eye irritation scores according to the modified Kay and Calandra scoring system

Animal

Time
(hours)

Cornea

Iris

Conjunctiva

Redness

Chemosis

Discharge

Rabbit 1

1

0

0

1

1

2

24

0

0

1

0

0

48

0

0

0

0

0

72

0

0

0

0

0

Rabbit 2

1

0

0

1

1

0

24

0

0

1

0

0

48

0

0

0

0

0

72

0

0

0

0

0

Rabbit 3

1

0

0

1

1

0

24

0

0

1

0

0

48

0

0

1

0

0

72

0

0

0

0

0

Rabbit 4

1

0

0

1

1

2

24

0

0

1

1

0

48

0

0

1

0

0

72

0

0

0

0

0

Rabbit 5

1

0

0

1

1

0

24

0

0

1

0

0

48

0

0

1

0

0

72

0

0

0

0

0

Rabbit 6

1

0

0

1

1

2

24

0

0

1

0

0

48

0

0

0

0

0

72

0

0

0

0

0

 

Mortality:

All animals survived to the scheduled necropsy

Applicant's summary and conclusion

Conclusions:
Based on the results of this study, MKH 3586 is classified as a minimal irritant to the rabbit eye.
Executive summary:

In a primary eye irritation study, 0.1 mL MKH 3586 was instilled into the conjunctival sac of the left eye of six young male adult New Zealand White rabbits. The right eye acted as a untreated control. Each treated eye was evaluated for irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours following treatment using the modified Kay and Calandra scoring system

 

No clinical signs of toxicity or other non-ocular lesions were observed. The cornea and iris showed no lesions or other signs of irritation. The test material caused transient conjunctival discharge (grade 2) as well as chemosis (grade 1) and redness (grade 1). These signs of irritation were present 1 hour after treatment and had resolved in all animals by 72 hours.

 

Based on the results of this study, MKH 3586 is classified as a minimal irritant to the rabbit eye.