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Description of key information

The test article was found to induce severe damage to eyes and to be corrosive to skin.

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:
14 Feb 1989 to 15 Feb 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): TK 10648
- Substance type: organic
- Physical state: liquid; insoluble in water
- Stability under test conditions: stable
- Storage condition of test material: room temperature
- Analytical purity: lab sample
- Lot/batch No.: EN 42441
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 2100-2380 g
- Housing: individually in metal cages
- Diet: ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20+/-3 °C
- Humidity: 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hours light cycle
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 flank.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
The animals were killed for animal protective reasons 24 hours after removing the bandage.
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: right flank
- Coverage: 12 - 16 cm2
- Type of wrap: The patches were loosely covered with an aluminum foil and held in place for 4 hours by an adhesive tape.

SCORING SYSTEM: OECD scoring system
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
The test article induced maximum irritant effects which were expected not to be reversible within 14 days. The animals were killed for animal protective reasons 24 hours after removing the bandage.
Other effects:
Moderate to severe losses of weight were detected in all animals at termination of the study 24 hours after removing the bandages.
Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
Based on the study results the substance is considered corrosive to skin.
Executive summary:

The test article induced maximum irritant effects which were expected not to be reversible within 14 days. The animals were killed for animal protective reasons 24 hours after removing the bandage. It has to be concluded that the test article has corrosive effects in albino rabbits. Moderate to severe losses of weight were detected in all animals at termination of the study 24 hours after removing the bandages.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
The procedure used was the test for eye irritants described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO). The test was performed on 3 male and 3 female rabbits of the Russian breed weighing 1.7 to 2.1 kg. The animals were housed individually in metal cages (overall dimensions 47 x 32 x 34 cm), were kept at a constant room temperature of 18 + 1 C°, at a relative humidity of 55 + 5% and on a 14 hour light cycle day. The animals had ad libitum access to standard rabbit food - NAFAG, Gossau SG - and water. Prior to treatment they were adapted to the laboratories for a minimum of 8 days. Only rabbits with normal ophthalmic findings were used for these tests.
The test material in an amount of 0.1 mL was inserted into the conjunctival sac of the left eye of the 6 rabbits and the lids were held open for a few seconds. The right eye was not treated and served as a control. In 3 of the 6 rabbits approximately 1 minute after treatment both eyes were rinsed with physiologic saline. The reactions were appraised with a slit lamp after 1 and 6 hours; 1; 2; 3, 6 and 8 days and scored for each individual rabbit.
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): FAT 81 004/A
- Substance type: organic
- Physical state: liquid
Species:
rabbit
Strain:
other: Russian breed
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.7 to 2.1 kg
- Housing: individually in metal cages (overall dimensions 47 x 32 x 34 cm)
- Diet: standard rabbit food - NAFAG, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: A minimum of 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 +/- 1 °C
- Humidity: 55 +/- 5 %
- Photoperiod: 14 hour light cycle
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
Duration of treatment / exposure:
single administration
Observation period (in vivo):
Up to 8 days
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: In 3 of the 6 rabbits approximately 1 minute after treatment both eyes were rinsed with physiologic saline.
- Time after start of exposure: 1 minute

SCORING SYSTEM: Cornea
A Opacity-degree of density (area most dense taken for reading)
No opacity 0
Scattered or diffuse area, details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Opalescent areas, no details of iris visible, size of pupil barely discernible 3
Opaque, iris invisible 4

B Area of cornea involved
One quarter (or less) but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area 4
A X B X 5 Total maximum = 80

Iris
A Values Normal 0
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) 1
No reaction to light, hemorrhage, gross destruction (any or all of these) 2
A X 5 Total maximum = 10

Conjunctivae
A Redness- (refers to palpebral and bulbar conjunctivae excluding cornea and iris) Vessels normal 0
Vessels definitely injected above normal 1
More diffuse, deeper crimson red, individual vessels not easily discernible 2
Diffuse beefy red 3

B.Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids about half closed to completely closed 4

C Discharge
No discharge , 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs, and considerable area around the eye 3
(A + B + C) X 2 Total maximum = 20

Calculation of the primary eye irritation index
The mean reaction scores for cornea, iris and conjunctiva observed after 6; 24 and 72 hours were summed up and the sum divided by 3.
This procedure was carried out separately for unrinsed (A) and rinsed (B) eyes respectively.
Index
0-10 minimal
11 - 25 moderate
26 - 55 slight
56 - 84 marked
above 84 extreme

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
2.9
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
iris score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Remarks:
unrinsed eyes
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
other: primary irritation index in rinsed eyes
Basis:
mean
Time point:
other: 6, 24 and 72 hours
Score:
ca. 65.7
Reversibility:
not reversible
Remarks on result:
other: Rinsing the eyes following instillation was of practically no effect.
Irritation parameter:
other: primary irritation index in unrinsed eyes
Basis:
mean
Time point:
other: 6, 24 and 72 hours
Score:
ca. 74.1
Reversibility:
not reversible
Irritant / corrosive response data:
The substance is severly irritant to eyes.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Executive summary:

In an acute eye irritation/corrosion study, single samples of 0.1 mL of the undiluted test article were instilled into one eye of each of six rabbits. In three animals, the eyes were washed out after 1 minute. The reactions were appraised with a slit lamp after 1 and 6 hours; 1; 2; 3; 6 and 8 days and scored for each individual rabbit. Under the conditions of this experiment the test preparation was found to cause marked irritation when applied to the rabbit eye mucosa. The irritation consisted of conjunctival reaction, reflex hyperemia of the iris and corneal reactions. The effects were not reversible within 8 days. Rinsing the eyes following instillation was of practically no effect.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

A guideline-compliant skin irritation test was performed with three New Zealand White rabbits according to OECD 404 (Ciba-Geigy, 1989). A 4-hour occlusive exposure to approximately 0.5 mL of the test material induced maximum irritant effects which were expected not to be reversible within 14 days. The animals were killed for animal protective reasons 24 hours after removing the bandage. It has to be concluded that the test article has corrosive effects in albino rabbits. Moderate to severe losses of weight were detected in all animals at termination of the study 24 hours after removing the bandages. A supporting study produced necroses even with a 5% test item dilution (Ciba-Geigy, 1982).

Eye Irritation

In an acute eye irritation/corrosion study, single samples of 0.1 mL of the undiluted test article were instilled into one eye of each of six rabbits (Ciba-Geigy, 1975). In three animals, the eyes were washed out after 1 minute. The reactions were appraised with a slit lamp after 1 and 6 hours; 1; 2; 3; 6 and 8 days and scored for each individual rabbit. Under the conditions of this experiment the test preparation was found to cause marked irritation when applied to the rabbit eye mucosa.The irritation consisted of conjunctival reaction, reflex hyperemia of the iris and corneal reactions.The effects were not reversible within 8 days. Rinsing the eyes following instillation was of practically no effect.

Justification for classification or non-classification

Based on the available information the test substance has to be classified as Skin Corr. 1C: H314: 'Causes severe skin burns and eye damage' in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.

Based on the available information the test substance has to be classified as Eye Dam. 1: H318: 'Causes serious eye damage' in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.