Benzene, 1-chloro-4-isocyanato-2-(trifluoromethyl)-

Eye irritation

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-chloro-4-isocyanato-2-(trifluoromethyl)benzene

EC Number:

608-783-6

Cas Number:

327-78-6

Molecular formula:

C8 H3 Cl F3 N O

IUPAC Name:

1-chloro-4-isocyanato-2-(trifluoromethyl)benzene

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

Results

Results 1

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'

Results 2

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'

Results 3

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'

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 5

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'

Results 6

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.