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Description of key information

Skin irritation (OECDTG 404): not irritant

Eye irritation (OECDTG 405): not irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 Aug 1985 - 16 Aug 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(adopted 12 May 1981)
GLP compliance:
yes
Specific details on test material used for the study:
- Chemical name: N-substituted toulene sulphonamide
- Trade name/code: Ketjenflex 8
- Impurity: Approx. 10% o/p toulene sulfonamide
- Specific gravity: Approx. 1200 kg/m3 (at 25 ̊ C)
- Solubility: Organic solvents except petroleum hydrocarbons
- Flash point: 224 ̊ C
- Boiling point: > 340 ̊ C
- Vapour pressure: < 1mm Hg at 150 ̊ C
- Appearance: Light yellow, viscous liquid
- Storage: At ambient temperature in the dark
- Stability: Practically unlimited
Species:
rabbit
Strain:
New Zealand White
Remarks:
SPF quality
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Obtained from The Broekman Institute, Someren,The Netherlands.
- Age at study initiation: Approximately 15 weeks old
- Weight at study initiation: 2750, 2701 and 2865 g
- Housing: In metal cages with perforated floors
- Diet (e.g. ad libitum): They were fed standard laboratory animal diet (100 g per day), obtained from Hope Farms, woerden (LK-01, pellet diameter 4mm)
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: Quarantine period was 7 days followed by an acclimation period of approximately 2.5 months

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): Relative humidity 50-70
- Photoperiod (hrs dark / hrs light): The artificial light sequence was 12 hours light, 12 hours dark.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): Undiluted

Duration of treatment / exposure:
Exposure duration was 4 hours
Observation period:
The exposed skin areas were examined for signs of erythema and oedema, and the responses were scored at 60 minutes, and approximately 24, 48 and 72 hours after removal of the dressing. For reference, the control site on the contralateral flank was used.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Test substance was applied to the right flank of each animal, the left flank being covered with the same dressing without test substance
- Coverage: approximately 10cm x 10 cm
- Type of wrap if used: gauze patch
- Administration: 0.5ml of the test substance was applied to a 6cm^2 gauze patch, which was attached with a drop of petrolatum to aluminum foil and mounted on permeable tape (Micropore, #M, St Paul, USA). This was then wrapped with flexible bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Remaining test substance was removed using a tissue moistened with tap water after exposure duration of 4 hours.

OBSERVATION TIME POINTS
- 60 minutes, 24 hours, 28 hours and 72 hours after removal of the dressing

SCORING SYSTEM:
- Method of calculation: Skin irritation grading system based on OECDTG 404 (1981)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Mean value
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Mean value
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Mean value
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Mean value
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Mean value
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Mean value
Irritant / corrosive response data:
The skin of all three animals showed no reactions. The primary irritation index was 0 ( total of 24 and 72 hours scores for erythema and oedema, divided by 6).
Interpretation of results:
other: Not classified
Remarks:
according to the EU classification criteria outlined in Annex I of 1272/2008/EC (CLP).
Conclusions:
Under the conditions of this test the skin of all three animals showed no reactions. The primary irritation index was 0.
Executive summary:

A skin irritation study was conducted according to OECD guideline 404, 1981, using the test material Ketjenflex 8 on the flank skin of 3 female New Zealand white strain rabbits. Each test site was treated with 0.5 ml of the undiluted test material for 4 hours using semiocclusive dressing. Observations for dermal irritation were made at 1, 24, 48 and 72 hours after removal of the patch. No significant test substance related effect was observed. The primary skin irritation index amounted to 0. Ketjenflex 8 can therefore be considered as non irritating to skin under the conditions of this study and does not have to be classified according to the EU classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 August 1985 - 22 August 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Adopted 12 May 1981
GLP compliance:
yes
Specific details on test material used for the study:
- Chemical name: N-substituted toulene sulphonamide
- Trade name/code: Ketjenflex 8
- Impurity: Approx. 10% o/p toulene sulfonamide
- Specific gravity: Approx. 1200 kg/m3 (at 25 ̊ C)
- Solubility: Organic solvents except petroleum hydrocarbons
- Flash point: 224 ̊ C
- Boiling point: > 340 ̊ C
- Vapour pressure: < 1mm Hg at 150 ̊ C
- Appearance: Light yellow, viscous liquid
- Storage: At ambient temperature in the dark
- Stability: Practically unlimited
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Obtained from The Broekman Institute, Someren,The Netherlands.
- Age at study initiation: Approximately 15 weeks old
- Weight at study initiation: 3378, 3165 and 3044 g
- Housing : In metal cages with perforated floors (RUCO, Valkenswaard).
- Diet (e.g. ad libitum): They were fed standard laboratory animal diet (100 g per day), obtained from Hope Farms, woerden (LK-01, pellet diameter 4mm)
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: Quarantine period was 7 days followed by an acclimation period of approximately 2.5 months

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22
- Humidity (%): Relative humidity 60-70
- Photoperiod (hrs dark / hrs light): The artificial light sequence was 12 hours light, 12 hours dark.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml of the test substance
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
Prior to dose administration, both eyes of the animals were inspected in order to detect any eye defect. Immediately after instillation of the test substance, the animals were observed and abnormalities were recorded. In addition, the eyes were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Grading of ocular lesions based on OECD 405 (1981)

TOOL USED TO ASSESS SCORE: fluorescein treatment
- a solution of 2% fluorescein in water (pH adjusted to 7.0) was applied to both eyes of each animal to examine quantitatively the potential for corneal injury
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Remarks:
swelling
Basis:
animal #1
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Remarks:
Redness
Basis:
animal #2
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
Mean Value
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
Mean value
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible
Irritant / corrosive response data:
One hour after instillation of the test substance swelling of the conjunctivae above normal was observed in all three animals. At the same time conjunctival redness was scored as grade 2 for two animals and grade 1 for the remaining animal. These signs were reversible since by the following day swelling had completely disappeared in all animals and redness was decreased to grade 1 in the remaining animal. 48 hours after instillations no more abnormal conjunctival redness or swelling was observed. No effects of the cornea and iris were observed in any of the animals. Treatment of the eyes with fluorescein 24 hours after instillation of the test substance did not reveal any epithelial damage in any of the animals.
Interpretation of results:
other: Not classified
Remarks:
according to the EU classification criteria outlined in Annex I of 1272/2008/EC (CLP).
Conclusions:
Under the conditions of this test, no effects of the cornea and iris were observed in any of the animals.
Executive summary:

To investigate the potential eye irritating effects of Ketjenflex 8, a study was conducted according to OECD 405 (adopted in 1981). 0.1 ml of the test substance was applied by instillation into one eye of, in total three female New Zealand White rabbits. No effects of the cornea and iris were observed in any of the animals. One hour after instillation moderate redness and mild was temporarily observed, however effects were reversible after 24 to 48 hours. Treatment of the eyes with fluorescein 24 hours after instillation of the test substance did not reveal any epithelial damage in any of the animals. Based on these results, it can be concluded that Ketjenflex 8 does not need to be classified as an eye irritant according to the EU classification criteria outlined in Annex I of 1272/2008/EC (CLP).

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion (OECD TG 405)

A skin irritation study was conducted according to OECD guideline 404, 1981, using the test material Ketjenflex 8 on the flank skin of 3 female New Zealand white strain rabbits. Each test site was treated with 0.5 ml of the undiluted test material for 4 hours using semiocclusive dressing. Observations for dermal irritation were made at 1, 24, 48 and 72 hours after removal of the patch. No significant test substance related effect was observed. The primary skin irritation index amounted to 0. Ketjenflex 8 can therefore be considered as non irritating to skin under the conditions of this study.

Eye irritation (OECD TG 405)

To investigate the potential eye irritating effects of Ketjenflex 8, a study was conducted according to OECD 405 (adopted in 1981). 0.1 ml of the test substance was applied by instillation into one eye of, in total three female New Zealand White rabbits. No effects of the cornea and iris were observed in any of the animals. One hour after instillation moderate redness and mild was temporarily observed, however effects were reversible after 24 to 48 hours. Treatment of the eyes with fluorescein 24 hours after instillation of the test substance did not reveal any epithelial damage in any of the animals. Based on these results, it can be concluded that Ketjenflex 8 does not need to be classified as an eye irritant.

Justification for classification or non-classification

Based on the available information, the substance N-Ethyl-o (or p)-toluenesulfonamide (NETSA) does not need to be classified for skin irritation and eye irritation, according to the classification criteria outlined in Annex I of 1272/2008/EC (CLP).