Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 Sep - 28 Sep 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Adopted in 1987
Deviations:
yes
Remarks:
Topical anesthetics/systemic analgesics not used; temperature and humidity in animal room slightly too high; more accurate description and scoring of corneal defects, and additional examination of aqueous humour. Deviations do not affect study outcome.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
448-100-7
EC Name:
-
Cas Number:
70441-63-3
Molecular formula:
C9H12FN
IUPAC Name:
4-fluoro-N-(propan-2-yl)aniline
Test material form:
liquid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Ltd., Wyton, Huntingdon, England
- Age at study initiation: adult, not further specified
- Body weight: 3.5, 3.7, and 3.6 kg
- Housing: Rabbits were individually housed in stainless steel cages with flat rod bases or plastic cages with perforated bases. Excrement trays beneath the cages contained low-dust (wood) bedding (type S 8/15, Ssniff Spezialdiäten GmbH, Soest, Germany).
- Diet: standard diet Ssniff K4 (Ssniff Spezialdiäten GmbH, Soest, Germany), approx. 100 - 120 g/animal/day; once per day in the morning.
- Water: tap water of drinking-water quality, ad libitum.
- Acclimation period: two weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23
- Humidity (%): 60 - 80
- Air changes (per hr): 12 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 Sep 1993 To: 21 Sep 1993 (Signs proved to be reversible within 7 days post exposure. Study was correctly terminated at this time point.)

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 100 µL
- Concentration: undiluted, pure test substance
Duration of treatment / exposure:
24 hours
Treatment was terminated by rinsing the treated eye with saline.
Observation period (in vivo):
Signs proved to be reversible within 7 days post exposure. Therefore, the study was terminated at this time point, and not continued until 21 days post exposure.
Reading time points: 1, 24, 48 and 72 h and 7 days
Number of animals or in vitro replicates:
3 female animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: 24 hours after instillation of the test substance the treated eye was rinsed with normal saline.
- Time after start of exposure: 24 hours

SCORING SYSTEM
Eye irritation was scored and recorded 1, 24, 48, and 72 h and 7 days post exposure. The effects in cornea, iris, and conjunctivae were assessed as described by Draize. The aqueous humour (opacity) was recorded as described by McDonald and Shadduck, 1987. In addition, any serious lesions or toxic effects other than ocular ones were recorded.

Corneal opacity - degree of density:
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 area, details of iris slightly obscured
3* = nacreous area, no details of iris visible, size of pupil barely discernible
4* = completely opaque cornea, iris not discernible through the opacity

Corneal opacity - area of opacity:
1 = 1/4 or less, but not 0
2 = more than 1/4, but less than 1/2
3 = more than 1/2, but less than 3/4
4 = more than 3/4 up to complete surface

Fluorescein staining (epithelial defects):
0 = absence of staining
1 = slight staining, underlying structures easily visible
2 = moderate staining, underlying structures easily visible, although there is some loss of detail
3 = marked staining, underlying structures barely visible but not completely obliterated
4 = extreme staining, underlying structures cannot be observed

To assess the area of fluorescein staining the criteria of "Corneal opacity - area of opacity" were used. In addition, differentiation was made between scattered punctate and confluent diffuse areas.

Iris:
0 = normal
1* = markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any of thereof, iris still reacting to light (sluggish reaction is positive)
2* = no reaction to light, haemorrhage, gross destruction (any or all of these)

Aqueous flare:
0 = light beam in the anterior chamber not visible (no Tyndall effect)
1 = Tyndall effect barely discernible, intensity of light beam in the anterior chamber less than intensity of light passing through lens
2 = Tyndall effect in the anterior chamber easily discernible, intensity of light beam egual to slit beam passing through lens
3 = Tyndall effect easily discernible, intensity of light beam greater than slit beam passing through lens

Conjunctivae - Erythema:
0 = blood vessels normal
1 = some blood vessels definitely hyperaemic (injected)
2* = diffuse, crimson colour, individual vessels not easily discernible
3* = diffuse, beefy redness

Conjunctivae - Chemosis (lids and/or nictitating membranes):
0 = no swelling
1 = any swelling above normal
2* = obvious swelling with partial eversion of lids (ectropium)
3* = swelling with lids about half closed
4* = swelling with lids more than half closed

Discharge:
0 = no discharge
1 = slightly increased discharge
2 = discharge with slight moistening of periorbital areas
3 = discharge with considerable moistening of periorbital areas

* Starred figures indicate a positive effect.

Only effects persisting for more than 24 hours were included in the evaluation. The irritation indices / mean irritation indices were calculated for cornea (degree of opacity), iris, erythema and swelling (chemosis) of the conjunctivae. Where three animals were used, interpretation was based on the individual indices obtained from the two most sensitive animals. Where there were delayed reactions, or where no irritation indices could be calculated (e.g. coloration by the test substance), other interpretation criteria were applied.


TOOL USED TO ASSESS SCORE
The examinations of cornea, iris and aqueous humour were facilitated using optical instruments (e.g. hand slit-lamp).
To define epithelial damage, one drop of a 1 % fluorescein solution was applied to the corneal surface 24 hours after administration of the test substance. The eye was then rinsed with normal saline to remove excess and nonabsorbed fluorescein. Evaluation was performed by means of ultraviolet illumination (area) in a darkened room and diffuse white illumination (intensity), according to McDonald and Shadduck, 1987. Where positive effects were recorded this procedure was repeated at the later observation times.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
Exposure of the test substance to the eye resulted in slight to moderate inflammatory reactions including discharge in all three animals. Additionally, in one animal mild effects of the cornea and iris were also transiently observed. All signs proved to be fully reversible within 7 days.

Any other information on results incl. tables

Table 1. Results of ocular irritation/corrosion testing with female New Zealand White rabbits exposed for 24 hours to N-Isopropyl-4-fluoroaniline

Animal no. Body weight (kg) Tissue/parameter examined Signs Draize grade after test substance application
1 h 24 h 48 h 72 h 7 d 14 d 21 d
1 3.5 cornea opacity 1 1 1 0 0 - -
area 3 3 3 0 0 - -
fluorescein intensity - 1 1 0 0 - -
area - 2c 1c 0 0 - -
iris   0 1 1 0 0 - -
conjunctivae redness 2 2 2 1 0 - -
swelling 1 2 3 2 0 - -
aqueous humour   0 0 0 0 0 - -
discharge   3 3 2 0 0 - -
2 3.7 cornea opacity 0 0 0 0 0 - -
area 0 0 0 0 0 - -
fluorescein intensity - 0 - - - - -
area - 0 - - - - -
iris   0 0 0 0 0 - -
conjunctivae redness 1 1 0 0 0 - -
swelling 1 1 0 0 0 - -
aqueous humour   0 0 0 0 0 - -
discharge   1 0 0 0 0 - -
3 3.6 cornea opacity 0 0 0 0 0 - -
area 0 0 0 0 0 - -
fluorescein intensity - 0 - - - - -
area - 0 - - - - -
iris   0 0 0 0 0 - -
conjunctivae redness 1 1 1 0 0 - -
swelling 1 0 0 0 0 - -
aqueous humour   0 0 0 0 0 - -
discharge   1 0 0 0 0 - -

- = not examined

c = confluent diffuse areas

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Exposure of the test substance to the eye resulted in slight to moderate inflammatory reactions including discharge in all three animals. Additionally, in one animal mild effects of the cornea and iris were also transiently observed. All signs proved to be fully reversible within 7 days. Based on the Draize scoring results and because of the full reversibility within 7 days, the test substance does not fulfill the criteria for classification and labeling as an eye irritant according to GHS.