Registration Dossier

Administrative data

Description of key information

4-Chlor-3-(trifluormethyl)-phenylisocyanate is irritating to skin and highly irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin 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
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
Himalayan
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Sex: male
- Source: LPT Laboratory of Pharmacology and Toxicology KG, 24601 Löhndorf, Germany
- Initial age: approx. 4.5 months
- Weight at study initiation: 2.1 - 2.3 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 20 days
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: moistened with water
Controls:
other: the surrounding untreated skin served as control
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approx. 6 cm²
- Type of wrap if used: gauze patch, non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing: no residual test item had to be removed
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to DRAIZE
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 - 10 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1 - 2
Max. score:
4
Reversibility:
fully reversible within: 8 - 10 days
Irritation parameter:
other: induration, laceration and peeling of skin
Basis:
other: all 3 animals
Time point:
other: 72 h up to day 11
Reversibility:
fully reversible within: 12 days
Remarks on result:
other: 72 hours after treatment induration of the skin became obvious which lasted up to and including day 7; laceration of the skin appeared on day 5 followed by peeling on days 8 to10 which lasted up to and including day 11.
Other effects:
No systemic intolerance reactions were observed.
Interpretation of results:
irritating
Remarks:
Migrated information
Executive summary:

In a dermal irritation study according to OECD TG 404 the test material was applied under semiocclusive conditions for 4 hours to the shaved skin of 3 rabbits. Skin irritation was assessed after 1, 24, 48 and 72 hours using the Draize scale. Erythema (grade 1) and oedema (grade 1 - 2) was observed in all animals 24 hours to days 7 - 10 after treatment. In addition, induration of the skin, laceration and peeling of the skin was noted in all animals. The effects partly lasted up to day 11 after patch removal. The test material should therefore be regarded as irritating to the skin of rabbits. No systemic intolerance reactions were observed.

According to classification criteria Butanoylanilin is an irritant to the skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
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
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
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.
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In a dermal irritation study according to OECD TG 404 the test material was applied under semiocclusive conditions for 4 hours to the shaved skin of 3 rabbits. Skin irritation was assessed after 1, 24, 48 and 72 hours using the Draize scale. Erythema (grade 1) and oedema (grade 1 - 2) was observed in all animals 24 hours to days 7 - 10 after treatment. In addition, induration of the skin, laceration and peeling of the skin was noted in all animals. The effects partly lasted up to day 11 after patch removal. The test material should therefore be regarded as irritating to the skin of rabbits. No systemic intolerance reactions were observed.

Eye irritation:

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.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the study results a classification with R 38 (irritating to skin) and R41 (risk of serious eye damage) according to Directive 67/548/EEC or with Skin Irrit. 2 (H315: causes skin irritation) and Eye Damage, Cat. 1 (H318: causes serious eye damage) according to Regulation (EC) No. 1272/2008 (CLP) is required.