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Description of key information

Reactive Brown 49 is non-irritating/corrosive to rabbit skin and rabbit 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:
key study
Study period:
October 6, 1998 to 03 Nov 1998
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:
not specified
Qualifier:
according to guideline
Guideline:
other: Directive 92/69 EEC, B.4. "Acute Toxicity - Skin Irritation", July 31, 1992.
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: TVR50
- Expiration date of the lot/batch: September 1, 2004

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (ca. 20°C) away from direct sunlight.
- Stability under test conditions: Stable at storage conditions.
- Stability of the test substance in the vehicle: Stable for 24 h in bidistilled water
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne
- Age at study initiation: 15 weeks
- Housing: Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
- Diet: Pelleted standard Provimi Kliba 3410 rabbit maintenance diet ad libitum (batch no. 62/98). Results of analysis are archived by RCC.
- Water: Community tap water from Itingen, ad libitum, in water bowls. Results of analysis are archived by RCC.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15 air changes per h
- Photoperiod (hrs dark / hrs light): by fluorescent light on a 12 h light/dark cycle.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Remarks:
bidistilled water
Controls:
other: opposite flank
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
24, 48 and 72 h
Number of animals:
1 male
2 females
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 rabbits
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 rabbit
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
mean score of 3 rabbit
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
IRRITATION : No signs of irritation were observed.

CORROSION : No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
COLORATION : Red staining by the test article of the treated skin was observed in all animals up to the end of the observation period.
VIABILITY/MORTALITY AND CLINICAL SIGNS :
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
Interpretation of results:
GHS criteria not met
Conclusions:
FAT 40'571/A is considered to be not irritating to rabbit skin.
Executive summary:

Primary skin irritation study with FAT 40571/A was carried out in New Zealand White according to OECD 404 and EU B 4 guideline with semi-occlusive type of coverage. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 h after removal of the dressing. The scores of each animal at the reading times 24, 48, 72 h were used in calculating the respective mean values for each type of lesion.

The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing by the number of data points. The primary irritation score was 0.00 (max. 8.0).

Local signs (mean values from 24 to 72 h) consisted of grade 0.00 erythema and grade 0.00 edema. No signs of irritation were observed. The test article caused red staining of the treated skin.

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

Based on the study results the test article FAT 40571/A 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:
Oct 13, 1998 to Nov 27,1998
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:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: TVR50
- Expiration date of the lot/batch: September 1,2004

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (ca. 20 °C) away from direct
sunlight
- Stability under test conditions: Stable at storage conditions
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne
- Age at study initiation: 15 weeks
- Weight at study initiation: male : 3069 g ; females : 3308 - 3190 g
- Housing: Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls, with wood and haysticks for gnawing.
- Diet: Pelleted standard Provimi Kliba 3410 rabbit maintenance diet ad libitum (batch no. 62/98). Results of analysis are archived by RCC.
- Water: Community tap water from Itingen, ad libitum, in water bowls. Results of analysis are archived by RCC.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): fluorescent light on a 12 h light/dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 g per animal
Duration of treatment / exposure:
The test article (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test article.
Observation period (in vivo):
Viability/mortality : Daily.
Clinical signs : Daily during the observation period.
Body weights : At start of acclimatization, on the first day of application and at termination of observation.
Scoring of irritation : performed approximately 1, 24, 48 and 72 h 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 h) were used in calculating the respective mean values for each type of lesion.
Number of animals or in vitro replicates:
3 (1 male, 2 females)
Details on study design:
The eyes of the animals were examined one day prior to test article administration. Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test.
On the day of treatment, the test article (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test article. The right eye remained untreated and served as the reference control. In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes (Washington, 1977).
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 animal
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 animal
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
3 animal
Time point:
24 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
3 animal
Time point:
48 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks:
Animal no 22
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
3 animal
Time point:
72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks:
Animal no 22 & 23
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 animal
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Effects on redness of eyes were reversible within 14 days but difficulties were seen during the first three days to score the eyes due to the staining caused by the substance.
No corrosion of the cornea was observed at any of the reading times.
Other effects:
COLORATION: Reversible orange staining of the cornea, iris, conjunctivae (including nictitating membrane) and lid hairs by the test article was observed.
Scleral and conjunctival (nictitating membrane) staining was not reversible in all animals after 21 days.

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

IRRITATION

Application of the test article to healthy rabbit conjunctivae resulted in a primary irritation score of 0.33. Slight swelling of the conjunctivae including nictitating membrane and slight watery discharge was observed in all animals one hour after treatment. Slight conjunctival reddening was noted until day 7 of the observation period.

COLORATION

Orange staining of the cornea, iris, conjunctivae (including nictitating membrane), lid hairs and sclera by the test article was observed. Scleral and conjunctival (nictitating membrane) staining was not reversible in all animals after 21 days.

BODY WEIGHTS

The body weight of all rabbits were considered to be within the normal range of variability.

Individual eye scores

Animal

Number

Time point

Cornea

Iris

Conjunctiva

Redness

Chemosis

22

24 h

0

0

*

0

23

0

0

*

0

24

0

0

*

0

22

48 h

0

0

1

0

23

0

0

*

0

24

0

0

*

0

22

72 h

0

0

1

0

23

0

0

1

0

24

0

0

*

0

 

*      : Reaction and/or staining prevented evaluation

Interpretation of results:
GHS criteria not met
Conclusions:
Based study results, the test substance is considered to be "not irritating" to the rabbit eye.
Executive summary:

The primary irritation potential of FAT 40'571/A was investigated in New Zealand White rabbits according to OECD 405 and B.5 guideline by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 h 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 h) were used in calculating the respective mean values for each type of lesion.

Eye irritation scores found in animal number 22 after 48 h, animal 23 after 72 h and 7 days. These effects were subsided after 14 days. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing the resulting total by the number of data points. The primary irritation score was 0.33 (max. 13). Swelling of the conjunctivae including nictitating membrane and watery discharge was observed in all animals one hour after treatment. Slight conjunctival reddening was noted until day 7 of the observation period. Orange staining of the cornea, iris, conjunctivae (including nictitating membrane), lid hairs and sclera of the treated eyes by the test article was observed.

Scleral and conjunctival (nictitating membrane) staining was not reversible after 21 days, all other staining effects were reversed after 21 days.

 

No corrosion was observed at any of the measuring intervals.

 

Based study results, the test substance is considered to be "not irritating" 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:

Primary skin irritation study with FAT 40571/A was carried out in New Zealand White according to OECD 404 and EU B 4 guideline with semi-occlusive type of coverage.The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 h after removal of the dressing. The scores of each animal at the reading times 24, 48, 72 h were used in calculating the respective mean values for each type of lesion.

The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing by the number of data points. The primary irritation score was 0.00 (max. 8.0).

Local signs (mean values from 24 to 72 h) consisted of grade 0.00 erythema and grade 0.00 edema. No signs of irritation were observed. The test article caused red staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Based on the study results the test substance is considered to be "not irritating" to rabbit skin

Eye irritation

The primary irritation potential of the FAT 40'571/A was investigated in New Zealand White rabbits according to OECD 405 and B.5 guideline by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 h 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 h) were used in calculating the respective mean values for each type of lesion.

Eye irritation scores found in animal number 22 after 48 h, animal 23 after 72 h and 7 days. These effects were subsided after 14 days.The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing the resulting total by the number of data points. The primary irritation score was 0.33 (max. 13). Swelling of the conjunctivae including nictitating membrane and watery discharge was observed in all animals one hour after treatment. Slight conjunctival reddening was noted until day 7 of the observation period. Orange staining of the cornea, iris, conjunctivae (including nictitating membrane), lid hairs and sclera of the treated eyes by the test article was observed. Scleral and conjunctival (nictitating membrane) staining was not reversible after 21 days, all other staining effects were reversed after 21 days.

 

No corrosion was observed at any of the measuring intervals.

 

Based study results, the test substance is considered to be "not irritating" to the rabbit eye.

Justification for classification or non-classification

Based on the findings in the skin and eye irritation study the test substance does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 to be irritating to skin or eyes.