Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
other information
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: male
- Source: LPT Laboratory of Pharmacology and Toxicology KG, 24601 Löhndorf, Germany
- Initial age: approx. 6.5 - 7.5 months
- Weight at study initiation: 2.4 - 2.7 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 20 days

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye, which remained untreated, served as control
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
eye was not rinsed after instillation of the test item
Observation period (in vivo):
1, 24, 48 and 72 hours and 4 to 21 days after instillation
Number of animals or in vitro replicates:
3

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days (1 animal)
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritation parameter:
iris score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 9 days
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #2
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 15 days
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 4 days
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritation parameter:
chemosis score
Basis:
animal: #2 and #3
Time point:
other: 24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritant / corrosive response data:
Under the present test conditions, a single application of 100 mg 4-Chlor-3-(trifluormethyl)phenylisocyanat per animal into the conjunctival sac of the right eye of three rabbits caused the following effects:

Corneal opacity (grade 1) was observed in all animals 1 hour to 72 hours after instillation, in animal no. 1 until 9 days, in animal no. 2 until 21 days after instillation. The fluorescein test performed after 24 hours revealed corneal staining in animal nos. 1 and 2 (3/4 of the surface) and animal no. 3 (1/2 of the surface). The fluorescein test performed after 7 days revealed corneal staining in animal nos. 1 and 2 (1/4 of the surface). The fluorescein test performed after 14 days revealed corneal staining in animal no. 2 (1/4 of the surface).

Irritation of the iris (grade 1) was noted in all animals 1 hour to 72 hours after instillation, in animal nos. 1 and 2 until 9 days after instillation.

Conjunctival redness (grade 1) was observed in all animals 1 hour to 48 hours after instillation, in animal nos. 1 and 2 until 15 days after instillation.
Conjunctival chemosis (grade 1) was observed in all animals hour to 24 hours after instillation, in animal no. 1 until 72 hours after instillation. In addition, white deposits in the conjunctival sac were observed in all animals 48 to 72 hours, in animal no. 1 until 4 days, in animal no. 2 until 5 days after instillation. Loss of hair on upper eyelid was observed in animal no. one 6 to 8 days, in animal no. two 6 to 9 days after instillation. Loss of hair on upper and lower eyelid was noted in animal no. one 9 to 21 days, in animal no. two 10 to 21 days after instillation. Secretion of the treated eye was observed in animal no. one 11 to 18 days after instillation.
Other effects:
No systemic intolerance reactions were observed.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information
Executive summary:

In an eye irritation study according to OECD TG 405 the test substance was instilled into the conjunctival sac of one eye of 3 male rabbits each. Eye irritation was assessed 1, 24, 48 and 72 hours and 4 to 21 days after instillation using the Draize scale. In this study slight irritation was seen as corneal opacity (grade 1), effects on iris (grade 1), conjunctional redness (grade 1) and conjunctional chemosis (grade 1). The cornea effects appeared to be not reversible within the 21 days observation period in one animal. Loss of hair at the upper and lower eye lid and white deposits in the conjunctival sac became obvious. No systemic intolerance reactions were observed.

According to classification criteria 4-Chlor-3-(trifluormethyl)-phenylisocyanat causes serious damage to rabbit's eyes.