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Administrative data

Description of key information

The test item is considered to be irritating to rabbits' skin and eye as shown in a primary skin and eye irritation study, respectively.

Exposure of rats to the test item at all dose levels caused signs indicative of respiratory tract irritation.

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:
December 20, 1994 - January 3, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farm, South Brunswick, NJ
- Housing: individually housing in in suspended stainless steel caging with mesh floors
- Diet: Pelleted Purina Rabbit Chow #5326
- Water: ad libitum (tap water)
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 - 22.2
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: The area of exposure was covered with a 2 1/4 x 3" adhesive-backed gauze patch and then wrapped with 3" Micropore tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Yes
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Skin reactions were scored at 1 hour, 24, 48 and 72 hours and 7, 10 and 14 days after patch removal.

SCORING SYSTEM:
- Method of calculation: according to Draize scoring
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
One hour after patch removal, well defined to moderate erythema and edema ware noted at all treated sites. Overall, The incidence and severity of irritation decreased with time. Although desquamation was evident at all sites between days 7 and 14, five of six animals were free from erythema and edema on day 14. Barely perceptible erythema remained at one site.
Other effects:
- Other adverse systemic effects: All animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test item is considered to be irritating to rabbits' skin as shown in a primary skin irritation study.
Executive summary:

A Primary Skin Irritation test was conducted with rabbits to determine the potential for the test item to produce irritation and/or corrosion after topical application. Five hundred milligram of the test substance was applied to the skin of six healthy rabbits for 4 hours. Following exposure, dermal irritation was evaluated by the method of Draize et al.

One hour after patch removal well defined to moderate erythema and edema were noted at all treated sites. Overall, the incidence and severity of irritation decreased with time.

The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 2.6, 2.0, 2.0, 2.3, 2.3 and 2.0, respectively. The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for edema were 3.0, 3.0, 2.6, 2.6, 2.0 and 2.3, respectively. Although desquamation was evident at all sites between days 7 and 14, five of six animals were free from erythema and edema on day 14. Barely perceptible erythema remained at one site. All animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.

Based on the results of testing, the test substance is considered to be irritating to rabbits‘ skin.

Endpoint:
skin corrosion: 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:
adverse effect observed (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:
January 13 and February 3, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farm, South Brunswick, NJ
- Housing: individually in suspended stainless steel caging mesh floors
- Diet: Pelleted Purina Rabbit Chow #5326
- Water: ad libitum (tap water)
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 – 21.7
- Photoperiod (hrs dark / hrs light): 12/12


Vehicle:
unchanged (no vehicle)
Controls:
other: left eye
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:
3 animals: washed after 20-30 seconds
(6 animals: unwashed)
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 washed (+6 unwashed)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Yes, at 3 of 9 animals
- Time after start of exposure: 20-30 seconds

SCORING SYSTEM: According to Draize scheme

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 17 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.6
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 17 days
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.6
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 17 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Within 24 hours of test substance instillation, all unwashed eyes exhibited corneal opacity, iritis and conjunctivitis. Overall, the incidence and severity of irritation decreased with time. Although iritis cleared from all eyes by day 17, conjunctivitis, pannus and/or corneal opacity persisted in 2 animals through day 21.
Other effects:
- Lesions and clinical observations: There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.
- Other observations: Twenty four hours after test substance instillation, all washed eyes exhibited conjunctivitis and iritis and corneal opacity were noted in one and two animals, respectively. The incidence and severity of irritation decreased with time. Iritis and corneal opacity cleared from all affected rabbits by 72 hours and day 4, respectively and all animals were free from ocular irritation by day 7.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Based on the results of a primary eye irritation test, the test item is considered to be irritating to rabbits' eye.
Executive summary:

A Primary Eye Irritation test was conducted with rabbits to determine the potential for the test item to produce irritation and/or corrosion via the ocular route. One-tenth of a milliliter of the test substance was instilled into one eye of nine healthy rabbits.The other eye remained untreated with the test substance and served as a control. The treated eyes of three rabbits were washed after instillation of the test substance. The eyes ol the remaining six rabbits were not washed.Ocular irritation was evaluated by the method of Draize et al. The eye scores were further classified by the system of Kay and Calandra (modified).

 

Within 24 hours of test substance instillation, all unwashed eyes exhibited corneal opacity, iritis and conjunctivitis. Overall, the incidence and severity of irritation decreased with time. Although iritis cleared from all eyes by day 17, conjunctivitis, pannus and/or corneal opacity persisted in 2 animals through day 21.

Twenty four hours after test substance instillation, all washed eyes exhibited conjunctivitis and iritis and corneal opacity were noted in one and two animals, respectively, The incidence and severity of irritation decreased with time. By day 7, all animals were free from ocular irritation.

 

Only data for the unwashed eyes were taken into account for the evaluation and classification as irritanting or non-irritanting to eye. The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for cornea opacity were 1.0, 1.0, 1.0, 1.0, 1.0 and 1.0, respectively. For iris, the individual mean scores were 0.3, 0.0, 1.0, 0.0, 1.0, and 1.0, respectively. The individual mean scores for conjunctivae were 3.0, 3.0, 2.6, 2.6, 3.0 and 2.3, respectively. The individual mean chemosis scores were 3.0, 3.0, 3.0, 2.6, 3.0 and 2.3, respectively.

Based on the results, the test item is considered to be irritating to rabbits' eye.

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:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation study

A Primary Skin Irritation test was conducted with rabbits to determine the potential for the test item to produce irritation and/or corrosion after topical application. Five hundred milligram of the test substance was applied to the skin of six healthy rabbits for 4 hours. Following exposure, dermal irritation was evaluated by the method of Draize et al.

One hour after patch removal well defined to moderate erythema and edema were noted at all treated sites. Overall, the incidence and severity of irritation decreased with time.

The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 2.6, 2.0, 2.0, 2.3, 2.3 and 2.0, respectively. The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for edema were 3.0, 3.0, 2.6, 2.6, 2.0 and 2.3, respectively. Although desquamation was evident at all sites between days 7 and 14, five of six animals were free from erythema and edema on day 14. Barely perceptible erythema remained at one site. All animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.

Based on the results of testing, the test substance is considered to be irritating to rabbits‘ skin.

Eye irritation study

A Primary Eye Irritation test was conducted with rabbits to determine the potential for the test item to produce irritation and/or corrosion via the ocular route. One-tenth of a milliliter of the test substance was instilled into one eye of nine healthy rabbits.The other eye remained untreated with the test substance and served as a control. The treated eyes of three rabbits were washed after instillation of the test substance. The eyes ol the remaining six rabbits were not washed.Ocular irritation was evaluated by the method of Draize et al. The eye scores were further classified by the system of Kay and Calandra (modified).

 

Within 24 hours of test substance instillation, all unwashed eyes exhibited corneal opacity, iritis and conjunctivitis. Overall, the incidence and severity of irritation decreased with time. Although iritis cleared from all eyes by day 17, conjunctivitis, pannus and/or corneal opacity persisted in 2 animals through day 21.

Twenty four hours after test substance instillation, all washed eyes exhibited conjunctivitis and iritis and corneal opacity were noted in one and two animals, respectively, The incidence and severity of irritation decreased with time. By day 7, all animals were free from ocular irritation.

 

Only data for the unwashed eyes were taken into account for the evaluation and classification as irritanting or non-irritanting to eye. The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for cornea opacity were 1.0, 1.0, 1.0, 1.0, 1.0 and 1.0, respectively. For iris, the individual mean scores were 0.3, 0.0, 1.0, 0.0, 1.0, and 1.0, respectively. The individual mean scores for conjunctivae were 3.0, 3.0, 2.6, 2.6, 3.0 and 2.3, respectively. The individual mean chemosis scores were 3.0, 3.0, 3.0, 2.6, 3.0 and 2.3, respectively.

Based on the results, the test item is considered to be irritating to rabbits' eye.

Repiratory irritation

In a short-term repeated dose toxicity study, signs of repiratory tract irritation were seen after inhalation with the test item (for more details please refer to IUCLID section 7.5.2).

Justification for classification or non-classification

Althoug the scoring system in these EPA studies differ from the EU scores normally used, based on the worst case result of these results of these studies, these studies are acceptable. Under the CLP regulation this leads to H317 (causes skin irritation) and H318 (causes severe eye irritation). Based on the repeated dose inhalation toxicity study, the test substance is considered to be classified as STOT SE cat. 3 and labelled with H335 (May cause respiratory irritation) according to Regulation REACH Regulation (EC) No 1272/2008.