Registration Dossier

Administrative data

Description of key information

The test substance does not have skin- or eye-irritating properties.

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:
13 January 1998 to 20 January 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Weight at study initiation: 3.1 - 3.8 kg
- Housing: Full air-conditioned rooms in separate cages arranged in a battery
- Diet (e.g. ad libitum): ssniff K-H (V2333), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): water from automatic water dispensers, ad libitum
- Acclimation period: 1 week under study conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Humidity (%): 50
- Photoperiod (hrs dark / hrs light): 12 hours daily

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Remarks:
deionized
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.4ml
Duration of treatment / exposure:
Exposure 4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5cm x 2.5 cm
- Type of wrap if used: surgical plaster

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: DRAIZE
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 3 days
Remarks on result:
probability of weak irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
30-60 minutes and 24 hours after removal of the plaster the animals showed moderate erythema. Very slight oedema were observed 24 hours after removal of the plaster. 48 and 72 hours after removal of the plaster the animals showed very slight up to well defined erythema. 7 days after removal of the plaster all irritations were reversible.

Based on the individual scores for erythema and oedema after 24, 48 and 72 hours, the following mean values were calculated: Erythema and eschar formation all animals : 1.7
animal 66 : 1.3
animal 67 : 2.0
animal 68 : 1.7

Oedema formation all animals : 0.3
animal 66 : 0.3
animal 67 : 0.3
animal 68 : 0.3

Based on the results of this study the substance is slightly irritating to skin.
Interpretation of results:
GHS criteria not met
Conclusions:
30-60 minutes and 24 hours after removal of the plaster the animals showed moderate erythema. Very slight oedema were observed 24 hours after removal of the plaster. 48 and 72 hours after removal of the plaster the animals showed very slight up to well defined erythema. 7 days after removal of the plaster all irritations were reversible.
Based on the results of this study the substance is slightly irritating to skin. The substance does not meet the EU criteria for classification on the basis of the effects noted.
Executive summary:

This study is read across to a close structural analogue, which is considered to be structurally equivalent to the substance to be registered, in that only the halogen ion differs. The study was conducted according to EU test guidance 92/69/EEC part B4 and OECD guideline 404 in compliance with GLP.

30-60 minutes and 24 hours after removal of the plaster the animals showed moderate erythema. Very slight oedema were observed 24 hours after removal of the plaster. 48 and 72 hours after removal of the plaster the animals showed very slight up to well defined erythema. 7 days after removal of the plaster all irritations were reversible.

Based on the individual scores for erythema and oedema after 24, 48 and 72 hours, the following mean values were calculated:

Erythema and eschar formation

animal #1 : 1.3

animal #2 : 2.0

animal #3 : 1.7

Oedema formation

animal #1 : 0.3

animal #2 : 0.3

animal #3 : 0.3

Based on the results of this study the substance is slightly irritating to skin. The substance does not meet the CLP criteria for classification on the basis of the effects 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:
20 April 2007 to 27 April 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species: Rabbit
Strain: New Zealand White rabbits
Source: TETRABBIT Kft., HUNGARY
Justification of strain: The New Zealand White rabbit is one of the standard species of acute irritation toxicity studies.
Animal health: Only animals in acceptable health condition were used for the test. Both eyes of each animal provisionally selected for testing were examined 24 hours prior to the start of study. Animals showing eye irritation, ocular defects or pre-existing corneal injury were not used.
Number of animals: 3 animals
Age of animals at arrivals: 10 weeks old, adult albino rabbit
Sex: male
Body weight range:
at the beginning of the study: 3378-3482 g
at the end of the study: 3555-3595 g
Date of receipt: 27 March 2007
Acclimatisation time: 24 days
Animal identification: The individual identification was performed by numbered ear tag. The cages were marked with individual identity cards with information about study code, sex, dose group, cage number and individual animal number.
Number of animal room: 618
Housing: Animals were housed individually in metal cages.
Lighting periods: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 20 ± 3 °C
Relative humidity: 30-70 %
Food and Feeding: Animals received PURINA Base – Lap gr. diet for rabbit produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum.
Water Supply: Animals will receive as tap water from automatic self- service water system ad libitum.
Quality Control of Water: The drinking water is routinely analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
The eyes of the test animals were not washed out after the application of test item.
Observation period (in vivo):
The eyes were examined at 1, 24, 48, 72 hours then one week after the treatment.
Number of animals or in vitro replicates:
3
Details on study design:
The eyes of the test animals were not washed out after the application of test item.
The eye irritation scores were evaluated according to the scoring system by Draize.
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:
all animals
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:
animal #1
Remarks:
mean value
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
mean value
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
mean value
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak 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:
The eyes were examined at 1, 24, 48, 72 hours then 1 week after the application.

One hour after treatment the vessels were diffuse and the individual vessels were not easily discernible (score 2), were found in all animals. In animal No.: 7171 the discharge with moistening of the lids and hairs, on considerable area around the eye (score 3) in other animal (No.: 7185) the discharge with moistening of the lids and hairs just adjacent to lids (score 2) occurred and in animal No.: 7159 the amount of discharge was greater than normal (score 1).

Chemosis was not observable during the study.

There were no effects observed in the cornea and iris during the study period.

24 hours after treatment some hyperaemic blood vessels (score 1) were observed in animal No.: 7159. In two cases (No.: 7185, 7171) the vessels were more diffuse (score 2).
Discharge alterations were not found at this time.

48 hours after treatment some blood vessels hyperaemic (score 1) were found in all animals.

72 hours after treatment in two animals (7185, 7171) the scores of the redness did not change compared to the previous observation. The animal No.: 7159 became fully symptom-free by this time.

1 week after treatment the study was terminated, since no primary irritation symptoms occurred.

During the study the control eyes of animals were symptom-free.

General state and the behaviour of animals were normal throughout the study period.

There were no notable body weight changes during the contact and observation period.

MEAN VALUES OF EYE IRRITATION SCORES FOR EU CLASSIFICATION

(24, 48, 72 hour reading)

 

Animal Number

Sex

Cornea Opacity

Iris

Conjunctivae

Redness

Chemosis

Discharge

7185

Male

0.00

0.00

1.33

0.00

0.00

7159

Male

0.00

0.00

0.66

0.00

0.00

7171

Male

0.00

0.00

1.33

0.00

0.00

Interpretation of results:
GHS criteria not met
Conclusions:
In conclusion, test item Gelb Sulfato applied to the rabbits' eye mucosa, caused temporary slight conjunctival reddening, which was fully reversible within one week. No other adverse effects were noted.
Consequently, the test substance is not an eye irritant.
Executive summary:

The acute eye irritation study of the test item Gelb Sulfato was performed in New Zealand White rabbits. The irritation effect of the test item was evaluated according to the Draize method.

 

The study was performed in accordance with the study plan, the OECD Guideline for Testing of Chemicals No. 405, Directive 2004/73/EEC B.5 and the Principles of Good Laboratory Practice (GLP) and is reported with a GLP certificate. The test item was placed into the conjunctival sac of left eye of each animal. The untreated right eye served as control. 0.1 g of the test item was used for the study in pure state, as a single dose. The eyes of the test animals were not washed out after the application of test item. The eyes were examined at 1, 24, 48, 72 hours then one week after the application.

One hour after the single application of test item Gelb Sulfato into the eye of the rabbits moderate redness and slightly to severely increased discharge were observed in the eye of the test animals. There were no effects observed in the cornea, iris and conjunctival chemosis during the study period. 72 hour after the application in two cases slight redness were found, one animal became fully symptom-free by this time. 1 week after treatment the study was terminated, since no primary irritation symptoms occurred.

During the study the control eyes of animals were symptom-free.  General state and the behaviour of animals were normal throughout the study period.

There were no notable body weight changes during the contact and observation period.

 

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:

cornea opacity : 0.00, 0.00, 0.00

iris : 0.00, 0.00, 0.00

redness : 1.33, 0.66, 1.33

chemosis : 0.00, 0.00, 0.00

discharge : 0.00, 0.00, 0.00

 

In conclusion, test item Gelb Sulfato applied to the rabbits' eye mucosa, caused slight to moderate conjunctival irritant effects, which were fully reversible within one week.

 

According to the EC criteria for classification and labelling requirements for dangerous substances and preparations, the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / Corrosion.

Two studies for skin irritation were used in a weight of evidence approach from 2 different very close structural analogues. both studies were conducted according to EU test guidance 92/69/EEC part B4 and OECD guideline 404 in compliance with GLP.

In the first study, 60 minutes after removal of the plaster the animals showed very slight erythema, which was no longer visible after 24 hours.

In the second study, 30-60 minutes and 24 hours after removal of the plaster the animals showed moderate erythema. Very slight oedema were observed 24 hours after removal of the plaster. 48 and 72 hours after removal of the plaster the animals showed very slight up to well defined erythema. 7 days after removal of the plaster all irritations were reversed.

Based on the results of these studies, it is concluded that the test substance is not irritating to skin. The substance does not meet the CLP criteria for classification on the basis of the effects noted.

 

Eye irritation.

The acute eye irritation study of the test item Gelb Sulfato was performed in New Zealand White rabbits. The irritation effect of the test item was evaluated according to the Draize method. The study was performed in accordance with the study plan, the OECD Guideline for Testing of Chemicals No. 405, Directive 2004/73/EEC B.5 and the Principles of Good Laboratory Practice (GLP) and is reported with a GLP certificate. The test item was placed into the conjunctival sac of left eye of each animal. The untreated right eye served as control. 0.1 g of the test item was used for the study in pure state, as a single dose. The eyes of the test animals were not washed out after the application of test item. The eyes were examined at 1, 24, 48, 72 hours then one week after the application.

One hour after the single application of test item Gelb Sulfato into the eye of the rabbits redness and increased discharge were observed in the eye of the test animals within the first 3 days after test substance administration. There were no effects observed in the cornea, iris and conjunctival chemosis during the study period. 72 hour after the application in two cases slight redness were found, one animal became fully symptom-free by this time. 1 week after treatment the study was terminated, since no primary irritation symptoms occurred.

During the study the control eyes of animals were symptom-free.  General state and the behaviour of animals were normal throughout the study period.

There were no notable body weight changes during the contact and observation period.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted to GLP an in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for irritation effects is therefore required.