Registration Dossier

Administrative data

Description of key information

Skin in vivo/Rabbits/ not irritating.
Eyes in vivo/ Rabbits/ not irritating.
Eyes in vitro/ Bovine eyes and Fertile White leghorn eggs/ slightly irritating.

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:
key study
Study period:
29 August 1989 to 5 September 1989.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
NO GLP methodology followed and this test was based on the OECD Guideline No. 404, adopted May 12, 1981, by the OECD council, and on Annex V, part B of Council Directive 7 9/831/EEC (Commission Directive 84/449/EEC of April 25, 1984; Official Journal L251, September 19, 1984).
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Approx. 12-14 weeks old
- Weight at study initiation: 2240 gr to 2990 gr
- Housing: The animals were housed individually in metal cages, identified by ear tattoo
- Diet (e.g. ad libitum): The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours light cycle day.

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: A control gauze patch moistened with distilled water was applied to the contralateral flanl.
Amount / concentration applied:
0.5 ml of the test article was applied to the right flank of each animal.
Duration of treatment / exposure:
4 hours
Observation period:
The skin reactions were evaluated 1, 24, 48 and 72 hours afetr removing the gauze patches.
Number of animals:
3 female rabbits
Details on study design:
An area of at least 36 cm2 was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch (approx. 12-16 cm2 ) bearing 0.5 ml of the test article was applied to the right flank of each animal. A control gauze patch moistened with distilled water was applied to the contralateral flank.
The patches were loosely covered with an aluminum foil (approx. 36 cm2 ) and held in place for 4 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg).

SCORING SYSTEM:
Erythema and eschar formation.
- No erythema: 0
- Very slight erythema (barely perceptible): 1
- Well defined erythema: 2
- Moderate to severe erythema: 3
- Severe erythema (beet redness) to slight eschar formation ( inj uries in depth): 4
Total possible erythema score 4

Edema formation
- No edema: 0
- Very slight edema (barely perceptible): 1
- Slight edema (edges of area well defined by definite raising): 2
- Moderate edema (raised approximately 1 nun): 3
- Severe edema (raised more than 1 mm and extending beyond area of exposure): 4
Total possible edema score 4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
662 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Non-irritant
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
876 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Non-irritant
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
984 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Non-irritant
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
662 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Non-irritant
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
876 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Non-irritant
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
984 female
Time point:
other: mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Non-irritant
Other effects:
All animals showed expected gain in body weight during the study.

Body weight (g):

 Animal N°  662/Female  876/Female  984/Female
 At strat of test  2990 gr.  2240 gr.  2450 gr.
 After 3 days  3030 gr.  2300 gr.  2530 gr.
 After 7 days (end)  3110 gr.  2370 gr  2650 gr.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the experimental conditions employed, FAT 92267/A is non-irritant to the skin rabbit.
Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit according to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

 

 Results

A single 4‑Hour, occlusive application of the test item to the intact skin of three females rabbits produced no erythema and no edema after patch removal and during the observation peiod. 

Conclusion

The test item produced a primary irritation index of 0.0 and was classified as non‑irritant to rabbit skin. No corrosive effects were noted.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 March 1991 to 25 March 1991.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP methodology followed and OCED guideline for Testing of Chemicals, Section 4, number 405, "Acute Eye Irritation / Corrosion" adopted February 24, 1987 was used to performed the experiment.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf.
- Age at study initiation: 14 weeks.
- Weight at study initiation: Male: 2.5 kg.
- Identification: By unique cage number and corresponding ear tag.
- Housing: Individually 1n a stainless steel cage equipped with an automatic cleaning and drinking system.
- Diet (e.g. ad libitum): Diet Pelleted standard Kliba 341, Batch 58/90 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum.
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum.
- Acclimation period: Four days under laboratory conditions after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C.
- Humidity (%): 40-70%.
- Air changes (per hr): Air conditioned with 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light / 12 hours dark, music during the light period.
Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remainded untreated and served as the reference control.
Amount / concentration applied:
0.1 ml of the (undiluted) test article was applied to the rabbit eye.
Duration of treatment / exposure:
One application
Observation period (in vivo):
The eye of the animal was examined for ocular irritation 1, 24, 48 and 72 hours and 7 days after administration.
Number of animals or in vitro replicates:
1 male
Details on study design:
- The eyes of the animal were examined once, one day prior to test article administration.
- Only those animal with no signs of ocular injury or irritation was used on the test.
- On test day 1, 0.1 ml of the (undiluted) test article was placed in the conjunctival sac of the left eye of the animal after gently pulling the lower lid
away from the eyeball. The lid was then gently held together for about one second to prevent loss of the test article.

SCORING SYSTEM:
EVALUATION OF EYE REACTIONS
CORNEAL IRRITATION:
Opacity: degree of density (densest area used for assessment)
- No ulceration or opacity: 0
- Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible: 1 *
- Easily discernible translucent area, details of iris slightly obscured: 2 *
- Nacrous area, no details of iris visible, size of pupil barely discernible: 3 *
- Opaque cornea, iris not discernible through the opacity: 4 *

IRIDIC IRRITATION:
- Normal: 0
- Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination thereof, Iris still
reacting to light (sluggish reaction is positive): 1 *
- No reaction to light, hemorrhage, gross destruction (any or al 1 of these): 2 *

CONJUNCTIVAL IRRITATION:
- Redness (refers to palpebral and bulbar conjunctivae, cornea and iris). Blood vessels normal 0
- Some blood vessels definitely hyperemic (injected) 1
- Diffuse, crimson color, individual vessels not easily discernible 2 *
- Diffuse beefy red 3 *

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

The maximum scores are:
Cornea : 4
Conjunctival Redness : ** 3
Iris : 2
Conjunctival Chemosis : ** 4

Maximum attainable score : 13


TOOL USED TO ASSESS SCORE:
Eye examinations were made with a slit-lamp 30 SL/M (C. Zeiss AG, Zuerich / Switzerland) and a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel /
Switzerland).
Irritation parameter:
other: Primary irritation index
Basis:
animal #1
Remarks:
63 male
Time point:
other: mean scores at 1,24, 48, 72 hours and 7 days after exposure
Score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
63 male
Time point:
other: mean values 24-72 hours
Score:
0.33
Reversibility:
not fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
63 male
Time point:
other: mean values 24-72 hours
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
63 male
Time point:
other: mean values 24-72 hours
Score:
1
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
63 male
Time point:
other: mean values 24-72 hours
Score:
1
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
IRRITATION
- FAT 92'267/A showed a primary Irritation score of: 3.00, when applied to the conjunctival sac of the rabbit eye.

CORROSION
- Slight diffuse corneal opacity was observed within 1 hour to 24 hours after test article application.
Other effects:
VIABILITY / MORTALITY AND CLINICAL SIGNS
No acute clinical signs were observed in the animal during the test and observation period, and no mortality occurred.

COLORATION
In the area of application no staining of the cornea and conjunctivae by pigment or coloring of the test article was observed.

BODY WEIGHTS
The body weight gain of the rabbit was within physiological limits.

INDIVIDUAL FINDINGS

hours/days after application

After 1 hour:

- Cornea: generally slight diffuse;

- Conjunctivae: generally severe erythema and edema;

- Nictitating membrane: generally reddened and swollen

- Sclera: blood vessels, generally slightly visible

- Discharge: lidhair, slightly wetted.

After 24 hours:

- Cornea: generally slight diffuse;

- Conjunctivae: generally slight erythema and edema;

- Nictitating membrane: generally reddened and swollen

- Sclera: blood vessels, generally clearly visible

After 48 hours:

- Conjunctivae: generally slight erythema and edema;

- Nictitating membrane: generally reddened and swollen

- Sclera: blood vessels, generally clearly visible

After 72 hours:

- Conjunctivae: generally slight erythema and edema;

- Nictitating membrane: generally reddened and swollen

- Sclera: blood vessels, generally clearly visible

After 7 days:

- Sclera: blood vessels, ventral visible

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the conditions of the experiment, the test article (FAT 92'267/A) had to be classified as not irritant to the rabbit eye.
Executive summary:

The purpose of this primary eye irritation study was to assess the possible irritation potential when a single dose of FAT 92'267/A was placed in the conjunctival sac of a rabbit eye. The experiment was donne according to the OCED guideline for Testing of Chemicals, Section 4, number 405, "Acute Eye Irritation / Corrosion" adopted February 24, 1987 was used to performed the experiment.

GLP methodology was follows during the test.

To performed this experiment, one New Zaeland White rabbit was used.

On test day 1, 0.1 ml of the (undiluted) test article was placed in the conjunctival sac of the left eye of the animal after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about one second to prevent loss of the test article.

The eye of the animal was examined for ocular irritation 1, 24, 48 and 72 hours and 7 days after administration.

Under the conditions of this experiment, FAT 92267/A was found to cause a primary irritation score of 3.00, when applied to the conjunctival sac of the rabbit eye.

Slight diffuse corneal opacity was observed within 1 hour to 24 hours after test article application.

In the area of application no staining of the cornea and conjunctivae by pigemnt or coloring of the test article was observed.

Conclusion:

Under the conditions of the experiment, the test article (FAT 92'267/A) had to be classified as not irritant to the rabbit eye.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation in vivo:

A study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit according to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

 A single 4‑Hour, occlusive application of the test item to the intact skin of three females rabbits produced no erythema and no edema after patch removal and during the observation peiod. 

The test item produced a primary irritation index of0.0and was classified as non‑irritant to rabbit skin. No corrosive effects were noted.

Eye irritation in vivo:

The purpose of this primary eye irritation study was to assess the possible irritation potential when a single dose of FAT 92'267/A was placed in the conjunctival sac of a rabbit eye. The experiment was donne according to the OCED guideline for Testing of Chemicals, Section 4, number 405, "Acute Eye Irritation / Corrosion" adopted February 24, 1987 was used to performed the experiment.

To performed this experiment, one New Zaeland White rabbit was used.

Under the conditions of this experiment, FAT 92267/A was found to cause a primary irritation score of 3.00, when applied to the conjunctival sac of the rabbit eye.

Slight diffuse corneal opacity was observed within 1 hour to 24 hours after test article application.

In the area of application no staining of the cornea and conjunctivae by pigemnt or coloring of the test article was observed.

Under the conditions of the experiment, the test article (FAT 92'267/A) had to be classified as not irritant to the rabbit eye.

Eye irritation in vitro:

The study was performed to assess the eye irritancy potential of the test article by means of the BECAM assay using isolated bovine

eyes (BE) and the chorioallantoic membrane (CAM) of hens' eggs.

No GLP methodolgy was followed to performed the experiment and there are no OECD and EEC guidelines and recommendations available for this test system.

The method is increasingly used for the detection of eye mucosa membrane irritants. Eye irritation caused by external contact

with chemical substances is characterized by corneal damage and/or conjunctival injury and/or iris defects.

Negative control:

The untreated eye and physiological saline-treated eggs showed no signs of irritation.

Positive control:

BE assay: Toluene: 1.5 and Acetone: 3.5

CAM assay: NaOH: 19.1 and SDS: 11.3

On account of these results, the BECAM assay was considered to be valid.

BE assay:

- Opacity: slight opacity in three cases, no opacity in two cases.

- Epithelial integrity: diffuse and weak epithelial integrity in one case, no epithelial integrity in four cases.

- Epithelial detachment: No epithalial detachment.

CAM assay:

- Haemorrhage: Haemorrhage in all cases.

- Lysis: No lysis

- Coagulation: No coagulation

BE assay mean score: 0.7 (slight)

CAM assay mean score: 3.0 (slight)

Final interpretation: slightly irritation.

The irritation of FAT 92'267/A in the BECAM assay was investigated and the test article revealed slight corneal damage in the bovine

eyes. The effects on the CAM were classified as slight.


Justification for selection of skin irritation / corrosion endpoint:
One study available.

Justification for classification or non-classification

Based on the available data on skin and eye irritation, the test substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC.