Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23rd July to 13th August 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in accordance with recognised guideline. Although no data is available on the study's GLP compliance equivalent quality assurance methods were in place at the testing laboratory. The substance is present in an oil formulation at ca.30%.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Remarks:
Quality assurance audit and study director statement included in the report

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Dinoseb (DNBP) in oil 300 g/l.
30-31.2% w/w DNBP.
DNBP formulation, a brown liquid, was received on 11 July 1984 and was stored at ambient temperature.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Pemberley Rabbits, Cottenham, Cambridgeshire.
- Age at study initiation: approximately 9 to 10 weeks of age
- Weight at study initiation: 2.1 to 2.3 kg
- Housing: the rabbits were individually housed in metal cages with perforated floors
- Diet/water (e.g. ad libitum): free access to tap water and SDS Standard Rabbit Diet
- Acclimation period: the rabbits selected for the study were all acclimated to the laboratory environment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 19°C
- Humidity (%): 30-70%
- Air changes (per hr): Air exchange was maintained at approximately 19 air changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
A 0.1 ml aliquot of DNBP formulation was placed into the lower everted lid of one eye of each animal.
Duration of treatment / exposure:
The eyelids were then gently held together for one second before releasing.
Observation period (in vivo):
Examination of the eyes was made after 1 hour and 1, 2, 3, 4, 7, 14 and 21 days after instillation. Observation of the eyes was aided by the use of a handheld torch.
Number of animals or in vitro replicates:
2 males and 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM:
Grading and scoring of the ocular lesions were performed using the prescribed numerical scoring system as follows:

Cornea: degree of density (area most dense taken for reading):

0 - No ulceration or opacity
1 - Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 - Easily discernible translucent areas, details of iris slightly obscured
3 - Nacrous areas, no details of iris visible, size of pupil barely discernible
4 - Opaque cornea, iris not discernible through the opacity


Iris:

0 - Normal
1 - Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 - No reaction to light, haemorrhage, gross destruction (any or all of these)


Conjunctivae:
Redness (refers to palpebral and bulbar conjunctivae cornea and iris):

0 - Blood vessels normal
1 - Some blood vessels definitely hyperaemic (injected)
2 - Diffuse, crimson colour, individual vessels not easily discernible
3 - Diffuse, beefy red

Chemosis (lids and/or nictitating membranes):

0 - No swelling
1 - Any swelling above normal (includes nictitating membranes)
2 - Obvious swelling with partial eversion of lids
3 - Swelling with lids about half-closed
4 - Swelling with lids more than half-closed

A note was also made of any lesion not covered by this scoring system.


TOOL USED TO ASSESS SCORE:
Observation of the eyes was aided by the use of a handheld torch.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 hours
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Reversibility of effects was seen in 2 animals but effects persisited in the 3rd animal
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48 hours
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Reversibility of effects was seen in 2 animals but effects persisited in the 3rd animal
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 hours
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Reversibility of effects was seen in 2 animals but effects persisited in the 3rd animal
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 & 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 & 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48 hours
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 72 hours
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
Corneal opacities developed in all three animals and persisted in one 21 days after instillation. Vascularization on the cornea was seen in two animals.
Iritis was seen in all three animals.
A diffuse crimson red colouration of the conjunctivae accompanied by considerable swelling with the eyelids about half-closed was seen in all three animals.
Other effects:
A copious discharge was also observed in all three animals.

Any other information on results incl. tables

Instillation of DNBP formulation into the rabbit eye elicited a positive response in all three treated animals according to OECD test criteria.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Instillation of DNBP formulation into the rabbit eye elicited a positive response in all three treated animals according to OECD test criteria.
The mean value of the scores for cornea opacity, iris lesions, redness & oedema of the conjuctivae, for 24, 48 and 72 hours was calculated. As lesions persisted to the end of the observation period at day 21, according to the dangerous substances directive, 67/548/EEC, the substance is classified as R41, Risk of serious damage to eyes.
Executive summary:

The primary eye irritation potential of the test material was evaluated when 0.1 mL was instilled into one eye of each of 3 rabbits.

Corneal opacities developed in all three animals and persisted in one 21 days after instillation. Vascularization on the cornea was seen in two animals. Iritis was seen in all three animals.

A diffuse crimson red colouration of the conjunctivae accompanied by considerable swelling with the eyelids about half-closed was seen in all three animals.

Instillation of DNBP formulation into the rabbit eye elicited a positive response in all three treated animals according to OECD test criteria.

The mean value of the scores for cornea opacity, iris lesions, redness & oedema of the conjuctivae, for 24, 48 and 72 hours was calculated. As lesions persisted to the end of the observation period at day 21, according to the dangerous substances directive, 67/548/EEC, the substance is classified as R41, Risk of serious damage to eyes.