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Description of key information

No effects were not in a primary skin irritation study. Irreversible pink staining of the nictitating membrane and the sclera was noted in the primary eye irritation study.

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:
Experiment start date - 30 March 1999; Experiment end date - 15 April 15 1999; Study completion date - 18 May 1999.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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 (incl. QA statement)
Specific details on test material used for the study:
Identity: FAT 40'574/B
Batch: WP 23/99
Purity: Approx 75%
Appearance: Solid, dark-red powder
Storage: At room temperature at about 20 °C
Expiration Date: 08 February 2006
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Age when treated: Females: 14 weeks; Males: 16 weeks
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, with target ranges for room temperature 22 ± 3°C and relative humidity 40-70% (values above 70% during cleaning process possible).
Room environment was monitored continuously with hourly recordings. The room was illuminated by fluorescent light on a 12 hour light/dark cycle. Recorded music was played for approximately 8 hours during the light period.
Accommodation: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
Water: Community tap water from Itingen, available ad libitum.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: The test substance was moistened with bidistilled water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 and 72 hours
Number of animals:
3
Details on study design:
Grading of Skin Reactions
ERYTHEMA AND ESCHAR FORMATION
No erythema................................................................................................................................ 0
Very slight erythema..................................................................................................................... 1
Well-defined erythema................................................................................................................... 2
Moderate to severe erythema......................................................................................................... 3
Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema reading...... 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 (edges raised approximately 1 mm)......................................................................... 3
Severe edema (raised more than 1 mm and extending beyond the area of exposure)............................. 4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 0.00
Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. No signs of irritation were observed.
Other effects:
COLORATION: Violet staining by the test article of the treated skin area was observed until study termination.

MORTALITY/CLINICAL SIGNS: No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

CORROSION: No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.

BODY WEIGHTS: The body weight of all rabbits were considered to be within the normal range of variability.
Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40574/B is not a skin irritant.
Executive summary:

The primary skin irritation potential of the test article was investigated by topical application of 0.5 g to 6 sq.cm intact dorsal skin of each of three young adult New Zealand White rabbits. This study was conducted according to OECD test guideline 404 in a GLP certified laboratory.

The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion.

The mean 24/48/72h erythema and edema scores was 0.00. Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. No signs of irritation were observed. The test article caused violet staining of the treated skin until the end of the observation period.

No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Based upon the referred classification criteria (EEC Commission Directive 93/21/EEC of April 27, 1993), the test article is considered to be "not irritating" to rabbit skin.

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:
Experiment start date - 07 April 1999; Experiment completion date - 03 May 1999; Study completion date - 11 May 1999.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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 (incl. QA statement)
Specific details on test material used for the study:
Identity: FAT 40574/B
Batch: WP 23/99
Purity: Approx 75 %
Appearance: Solid, dark-red powder
Storage: At room temperature at about 20 °C
Expiration Date: 08 February 2006
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Age when treated: Females: 14 weeks; Males: 15 weeks
Identification: By unique cage number and corresponding ear number.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, with target ranges for room temperature 22 ± 3 °C and relative humidity 40-70 % (values above 70 % during cleaning process possible). Room environment was monitored continuously with hourly recordings. The room was illuminated by fluorescent light on a 12 hour light/dark cycle. Recorded music was played for approximately 8 hours during the light period.
Accommodation: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
Water: Community tap water from Itingen, available ad libitum.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
Single application in the conjunctival sac
Observation period (in vivo):
1, 24, 48 and 72 hours as well as 7, 14 and 21 days after treatment.
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM:
CORNEA
Opacity: degree of density (area most dense taken for reading)
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
Nacreous area, no details of iris visible, size of pupil barely discernible..................... 3
Opaque cornea, iris not discernible through the opacity........................................... 4

IRIS
Normal..................................... 0
Markedly deepened rugae, congestion, swelling, moderate circumcomeal hyperemia, or injection, any 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

CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae when compared with control eye)
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 (including 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

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Reversibility of any observed effect: Changes not fully reversible within 21 days
Other effects:
COLORATION: Irreversible pink staining of the nictitating membrane and the sclera was noted in all animals until study termination on day 21.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Pink staining nictitating membrane and the sclera by the test article was observed in all animals until 21 days after treatment. Based on the findings of this study, FAT 40574/B was classified as Eye corrosion - 1.
Executive summary:

The primary irritation potential of the test article was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. This study was conducted according to OECD test guideline 405 in a GLP-certified laboratory. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours as well as 7, 14 and 21 days after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. The 24/48/72h eye irritation scores were recorded. In all animals, slight to moderate swelling of the conjunctivae, as well as slight watery discharge were observed one hour after treatment. In two animals, conjunctival reddening was noted after 24 hours and persisted in one animal until 48 hours after treatment. All signs of irritation were reversible after 72 hours. The 24/48/72 h corneal opacity, iris, conjuctivae and chemosis score was 0, 0, 0.33, 0, respectively. Pink staining nictitating membrane and the sclera by the test article was observed in all animals until 21 days after treatment. Based on the findings of this study, FAT 40574/B was classified as Eye corrosion - 1.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation


The primary skin irritation potential of the test article was investigated by topical application of 0.5 g to 6 sq.cm intact dorsal skin of each of three young adult New Zealand White rabbits. This study was conducted according to OECD test guideline 404 in a GLP certified laboratory. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion. The mean 24/48/72h erythema and edema scores was 0.00. Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. No signs of irritation were observed. The test article caused violet staining of the treated skin until the end of the observation period. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Based upon the referred classification criteria (EEC Commission Directive 93/21/EEC of April 27, 1993), the test article is considered to be "not irritating" to rabbit skin.


Eye irritation


The primary irritation potential of the test article was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. This study was conducted according to OECD test guideline 405 in a GLP certified laboratory. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours as well as 7, 14 and 21 days after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. The 24/48/72h eye irritation scores were recorded. In all animals, slight to moderate swelling of the conjunctivae, as well as slight watery discharge were observed one hour after treatment. In two animals, conjunctival reddening was noted after 24 hours and persisted in one animal until 48 hours after treatment. All signs of irritation were reversible after 72 hours. The 24/48/72 h corneal opacity, iris, conjuctivae and chemosis score was 0, 0, 0.33, 0 respectively. Pink staining nictitating membrane and the sclera by the test article was observed in all animals until 21 days after treatment. Based on the findings of this study, FAT 40574/B was classified as Eye corrosion - 1.

Justification for classification or non-classification

Due to irreversible pink staining of the nictitating membrane and the sclera until study termination on day 21, the substance does need to be classified as Eye Damage 1 H318: causes severe eye damage. But no classification for skin irritation/corrosion is required.

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