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Description of key information

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:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
GLP compliance:
yes
Specific details on test material used for the study:
Proxel Press Paste
BX228, CofA Reference 9211301
Purity 74.3%
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Weight 3587-4825 g.
Type of coverage:
semiocclusive
Vehicle:
water
Controls:
other: each animal serves as its own control
Amount / concentration applied:
Concentration in vehicle: 1 g/ml
Total volume applied 0.5 ml
Duration of treatment / exposure:
4 hour(s)
Observation period:
The animals were assessed for up to 4 days
Number of animals:
6
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
Very slight or well defined erythema was present on the application sites of all animals for up to and including Day 2 or 3.Very slight oedema was present on 5 of the 6 animals after decontamination. This persisted in 2 animals for a further 2 or 3 days.
Conclusions:
Materials and methods
A sample of PROXEL Press Paste was assessed for its skin irritation potential according to US EPA PAG 81-5.
A group of six male rabbits received a single four-hour application of 500 mg (moistened with 0.5 mL water) of the test sample to the shorn flank. The animals were assessed for up to 4 days for any signs of skin irritation.

Results and discussion
Following a single four-hour application, very slight or well defined erythema was present on the application sites of all animals for up to and including Day 2 or 3. Very slight oedema was present on 5 of the 6 animals after decontamination. This persisted in 2 animals for a further 2 or 3 days. No other signs of irritation were seen.

Conclusion
PROXEL Press Paste was a slight irritant to rabbit skin, following a single four-hour application.
Executive summary:

A study was conducted to determine the skin irritation potential of the substance in rabbits according US EPA Guideline OPP 81 -5. A group of six male rabbits received a single four-hour application of 500 mg (moistened with 0.5 mL water) of the test sample to the shaved flank. The animals were assessed for up to 4 days for any signs of skin irritation. Very slight or well defined erythema was observed on the application sites of all animals up to Day 2 or 3. Very slight oedema was present on 5 of the 6 animals, which persisted in 2 animals till Day 3.  No other signs of irritation were seen. Under the study conditions, the substance was not considered to be irritating to rabbit skin (Robinson, 1993).

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
Batch number: GK 100 B
Species:
rabbit
Type of coverage:
semiocclusive
Vehicle:
water
Amount / concentration applied:
Concentration: 0.5 g
Duration of treatment / exposure:
72 hour(s)
Number of animals:
3
Details on study design:
The potential of BIT to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 g of the test material to the closely-clipped dorsa of three New Zealand White rabbits for four hours. Dermal reactions were assessed 1, 24, 48 and 72 hours after removal of the dressings.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible

No irritant response was observed at the test site of any animal at any time during the 72 hour observation period. The test sites of two animals were

stained orange and the third was stained yellow at the one hour examination.
BIT was classified as ‘non-irritant’ to skin.

Conclusions:
No irritant response was observed at the test site of any animal at any time during the 72 hour observation period. The test sites of two animals were
stained orange and the third was stained yellow at the one hour examination. BIT was classified as ‘non-irritant’ to skin.
Classification: not irritating
Executive summary:

A study was conducted to determine the skin irritation potential of the substance in rabbits according to a method similar to OECD Guideline 404. A group of three male rabbits received a single four-hour application of 500 mg (moistened with 0.5 mL water) of the test sample to the shaved flank. The animals were assessed for up to 4 days for any signs of skin irritation. No sign of dermal irritation was observed in any of the test animals at any time point. Under the study conditions, the substance was not considered to be irritating to rabbit skin (Rees, 1993).

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Principles of method if other than guideline:
Method: other: INVITTOX Protocol No 124. In-vitro Bovine Corneal Opacity and Permeability Assay (BCOP).
GLP compliance:
yes
Specific details on test material used for the study:
Batch LHW 1355
>99%
Species:
other: In-vitro Bovine Corneal Opacity and Permeability Assay (BCOP)
Vehicle:
physiological saline
Amount / concentration applied:
other: 7500, 750 and 75 ppm
Duration of treatment / exposure:
2 hour(s)
Details on study design:
The eye irritancy potential of 1,2-benzisothiazolin-3-one was assessed using the in-vitro BCOP assay at concentrations of 75, 750 and 7500 ppm. 1,2-benzisothiazolin- 3-one was found to be non-irritant using the in-vitro scoring method at the dilutions tested. This is comparable to the minimal score in the corresponding Dralze assay. A 7500 ppm solution of 1,2-benzisothiazolin-3-one was prepared as its sodium salt. The pH of the solution was adjusted to 8.43, being the pH nearest neutral at which this concentration of BIT was soluble. BIT was tested at 7500 ppm, 750 ppm and 75 ppm. Each dilution was tested in the experimental system on a separate day (n=9) against negative (saline) and positive (ethanol) controls. The In-vitro Scores obtained were related to the Dralze classification system.

Comment: other: the procedure was conducted 9 times at each concentration
Irritation parameter:
in vitro irritation score
Run / experiment:
7500 ppm
Value:
3.012
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
in vitro irritation score
Run / experiment:
750 ppm
Value:
0.666
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Irritation parameter:
in vitro irritation score
Run / experiment:
75 ppm
Value:
-0.207
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

BIT was found to be non-irritant using the in-vitro scoring method when tested at dilutions of 75 ppm, 750 ppm and 7500 ppm. This is comparable to the minimal score in the corresponding Draize assay.

Conclusions:
BIT was found to be non-irritant using the in-vitro scoring method when tested at dilutions of 75 ppm, 750 ppm and 7500 ppm. This is comparable to the minimal score in the corresponding Draize assay.
Executive summary:

The acute eye irritation potential of the substance was determined according to a method similar to OECD Guideline 437. The in vitro bovine corneal opacity assay was performed with the substance at concentrations of 0, 75, 750 and 7500 ppm. The in vitro irritation scores of the test concentrations were found to be 3.012, 0.666 and -0.207 respectively for 7500, 750 and 75 ppm. Under the study conditions, no prediction of eye irritation could be made based on the score of 3.012 at the highest test concentration (Smith, 2003).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

A study was conducted to determine the skin irritation potential of the substance in rabbits according US EPA Guideline OPP 81 -5. A group of six male rabbits received a single four-hour application of 500 mg (moistened with 0.5 mL water) of the test sample to the shaved flank. The animals were assessed for up to 4 days for any signs of skin irritation. Very slight or well defined erythema was observed on the application sites of all animals up to Day 2 or 3. Very slight oedema was present on 5 of the 6 animals, which persisted in 2 animals till Day 3.  No other signs of irritation were seen. Under the study conditions, the substance was not considered to be irritating to rabbit skin (Robinson, 1993).

A study was conducted to determine the skin irritation potential of the substance in rabbits according to a method similar to OECD Guideline 404. A group of three male rabbits received a single four-hour application of 500 mg (moistened with 0.5 mL water) of the test sample to the shaved flank. The animals were assessed for up to 4 days for any signs of skin irritation. No sign of dermal irritation was observed in any of the test animals at any time point. Under the study conditions, the substance was not considered to be irritating to rabbit skin (Rees, 1993).

Eye irritation:

A study was conducted to determine the eye irritation potential of the substance according to a method similar to US EPA Guideline OPP 81-4.  In accordance with a stepwise approach to ocular irritation assessment, a low volume of the test substance (10 mg) was applied to one of a male rabbit initially. As the reaction seen in this animal was less than severe, another animal was dosed with a full volume application (100 mg) of the test substance. The other eye was untreated (control eye). Immediately after the application of the test sample, an assessment of the initial pain reaction of the rabbit was made using a six-point scale. Approximately one week later, a second animal was dosed in a similar manner, with a full volume (100 mg) application of the test substance. The eyes were examined and the Draize scale was used to assess the grade of ocular reaction. In addition, as an aid in the assessment of corneal damage, fluorescein staining was used. Low volume application of the test substance caused moderate initial pain to the eye. No corneal or iridial effects were observed. Conjunctival effects included slight to moderate redness, slight to mild chemosis and slight discharge, which persisted till Day 4. Other signs of irritation included erythema and dried secretions on the eyelids, mucoid discharge, haemorrhaging of the nictitating membrane and superficial erosion of the corneal epithelium. Full volume application of the test substance caused moderate initial pain. Corneal and iridial effects could not be assessed due to severe swelling of the conjunctival sac. Other conjunctival effects included severe redness and severe discharge. After approximately 3 hours the degree of conjunctival swelling increased and lead to rupture of the conjunctival sac with severe redness and discharge. Other effects included mild corneal opacity, slight iritis, erythema on the eyelids, hemorrage of the nictitating membrane and constricted pupil. The animal was removed from the study and humanely sacrificed. Under the study conditions, based on the severe corrosive reactions observed following full volume application, the substance was considered to be causing serious eye damage to rabbit eye (Robinson, 1993).

The acute eye irritation potential of the substance was determined according to a method similar to OECD Guideline 437. The in vitro bovine corneal opacity assay was performed with the substance at concentrations of 0, 75, 750 and 7500 ppm. The in vitro irritation scores of the test concentrations were found to be 3.012, 0.666 and -0.207 respectively for 7500, 750 and 75 ppm. Under the study conditions, no prediction of eye irritation could be made based on the score of 3.012 at the highest test concentration (Smith, 2003).

Justification for classification or non-classification

Based on the in vivo skin irritation and in vivo and in vitro eye irritation studies with the substance, a classification as Eye Damage 1 (H318: Causes serious eye damage) is warranted according to EU CLP (1272/2208) criteria.