Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: The test item was demonstrated to be non-irritant in an in vivo study in rabbits performed according to OECD guideline 404 and EU Method B.4 and conform GLP requirements (Vasquez, 2012).

 

Eye irritation: The test item was demonstrated to be non-irritant to eyes in an in vivo study in rabbits performed according to OECD guideline 405 and EU Method B.5 and conform GLP requirements (Vasquez, 2012).

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:
From 5 December 2010 to 10 December 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Well documented study according to OECD guideline 439 and EU Method B.4. Limited information available on test item
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Remarks:
according to Good Laboratory Practice Regulations 21 CFR 58 (FDA), 40 CFR Part 792 (EPA-TSCA), and the OECD Principles [ENV/MC/CHEM(98)17]
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: not available
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was applied neat

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Millbrook
- Age at study initiation: 12 weeks
- Weight at study initiation: 2.7 to 3.0 kilograms
- Housing: indiviudally housed in compliance with USDA Guidelines. No other species were kept in the same room
- Diet (e.g. ad libitum): all animals had access to PMI Certified Hi-Fiber Rabbit Diet #5325.
- Water (e.g. ad libitum): ad libitum, tap water, via an automatic watering device
- Acclimation period: minimum of 5 days prior to dosing. During the acclimation period, each rabbit was observed at least once daily for any abnormalities or for the development of infectious desease. Only animals that were determined to be suitable for use were assigned to this study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20°C
- Humidity (%): 25 to 48%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
not specified
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
3 minutes, 60 minutes and 4 hours
Observation period:
3 days (after patch removal)
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 5 cm x 5 cm
- % coverage: no data
- Type of wrap if used: the test article was applied to an area (approximately 5 cm x 5 cm) on the dorsal trunk of each animal and covered with a gauze patch. The patch was lossely held in contact with the skin. The truk of the animal was wrapped with an elastic bandage dressing, which was held in place with non-irritating tape for the duration of the exposure period.
- Within 24 hours before initiation of the test, fur was removed from the dorsal trunk of each animal by clipping. Care was taken to avoid abrading the skin. Only animals with healthy skin were used. The animals were clipped as deemed necessary during the study to facilitate observations.
- In the interest of animal welfare the test began with the application of the test article to three intact test sites on a single animal. The first site was dosed and the patch was removed after 3 minutes and the response was graded. Since no serious skin reaction was observed, the second and third sites were dosed and the second patch was removed 1 hour and the repsonse was graded. Since the observations at this stage indicated that a four-hour exposure was necessary and could be humanely conducted, the third site patch was removed 4 hours after its application and the response was graded.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, residual test article was removed using mineral oil and gauze, without altering the existing response or the integrity of the epidermis.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- Mortality/morbidity: once daily
- Clinical observations: prior to dose administration and then daily
- Dermal observations:
3 minute and 60 minute sites: the animal was examined for signs of erythema and edema and the responses scored immediately after patch removal and at 30-60 minutes, and daily through Day 4.
4 hour sites: animals were examined for signs of erythema and edema and the responses scored at 30-60 minutes, 24, 48 and 72 hours (+/- 1 hour) after patch removal.
- Body weight: prior to dose administration and after the final skin grading.

SCORING SYSTEM:
- Dermal irritation was scored according to Draize. In addition to the observation of irritation, any lesions and other signs of toxicity were described.
Irritation parameter:
erythema score
Remarks:
3 minute exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Remarks:
3 minute exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Remarks:
1 hour exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
1 hour exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Remarks:
4 hour exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
4 hour exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Remarks:
4 hour exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
4 hour exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Remarks:
4 hour exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Remarks:
4 hour exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
- 3 minute exposure: no erythema and no edema; no other skin response observed.
- 60 minute exposure: well-defined erythema and no edema; no other skin response observed.
- 4 hour exposure: well-defined erythema with slight edema: no other skin response observed
Other effects:
Mortality/clinical observations:
- No mortality was observed during the study. No clinical signs were recorded during the course of the study.

Body weight:
Mean initial body weight ± SD: 2.8 ± 0.15 kg
Mean final body weight ± SD: 2.9 ± 0.12 kg
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was found to be non-irritating to the skin of rabbits according to the EEC Irritation Rating and the GHS Classification was also non-irritating.
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:
From 2010-12-15 to 2010-12-20
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Well documented study according to OECD Guideline 405 and EU Method B.5. Limited information available on test article.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Remarks:
according to Good Laboratory Practice Regulations 21 CFR 58 (FDA), 40 CFR Part 792 (EPA-TSCA) and the OECD Principles [ENV/MC/CHEM(98)17]
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: not available
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was applied neat as received from the sponsor.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Millbrook
- Age at study initiation: 13 weeks
- Weight at study initiation: 2.6 to 2.9 kilograms
- Housing: individually housed in compliance with USDA Guidelines. No other species were kept in the same room.
- Diet (e.g. ad libitum): all animals had access to PMI certified Hi-Fiber Rabbit Diet #5325.
- Water (e.g. ad libitum): ad libitum, tap water, via an automatic watering device.
- Acclimation period: a minimum of 7 days prior to dosing. During the acclimation period, each rabbit was observed at least once daily for any abnormalities or for the development of infectious disease. Only animals that were determined to be suitable for use ware assigned to this study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 21°C
- Humidity (%): 25 to 58%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye was left untreated
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single application
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eyes remained un-rinsed after instillation of the test article

SCORING SYSTEM:
- The grades of ocular reaction were scored according to Draize.
- An animal exhibited a positive reaction if the test article produced at any observation one or more of the following signs: opacity of the cronea (other than a slight dulling of the normal luster), inflammation of the iris (other than a slight deepening of the rugae or a light hyperemia of the circumcorneal blood vessels) or an obvious swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids or a diffuse crimson color with individual vessels not easily discernible.

TOOL USED TO ASSESS SCORE: no data
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No corneal, iris or conjunctivae irritation was observed in the untreated eyes of the rabbits at any time point. No corneal or iris irritation was observed in the treated eyes of the rabbits at any time point. Conjunctival redness and chemosis (scores of '1') were observed at 1 and 24 hours post dose with only one score of '1' observed at 48 hours for redness. Scores of '2' for discharge were observed at 1 hour. All three animals were observed to be normal at 72 hours and the study was terminated.
Other effects:
Mortality/clinical observations:
- No mortality or adverse clinical signs were observed in the animals during the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was found to be non-irritating to the eye according to the EEC and GHS criteria.
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

One reliable (Klimisch 2) in vivo study is available (Vasquez, 2012). This study in rabbits was performed according to OECD guideline 404 (Acute Dermal Irritation/Corrosion) and EU Method B.4 (Acute Toxicity: Dermal Irritation/Corrosion) and conform GLP requirements. After 3 minutes of exposure, no erythema and no edema were observed. After 60 minutes of exposure, well-defined erythema and no edema was observed. After 4 hours of exposure well-defined erythema with slight edema was observed. No other skin responses were noted after the 3 minutes, 60 minutes and 4 hour exposure. Based on these results, the test item is considered not classified according to the CLP Regulation.

 

Eye irritation

One reliable (Klimisch 2) is available (Vasquez, 2012) was performed according to OECD guideline 405 (Acute Eye Irritation/Corrosion) and EU Method B.5 (Acute Toxicity: Eye Irritation/Corrosion) and conform GLP requirements. No corneal or iris irritation was observed in the treated eyes of the rabbits at any time point. Conjunctival redness and chemosis (scores of '1') were observed at 1 and 24 hours post dose with only one score of '1' observed at 48 hours for redness. Scores of '2' for discharge were observed at 1 hour. All three animals were observed to be normal at 72 hours. The test substance was found to be non-irritating to the eye according to the CLP Regulation.

Justification for classification or non-classification

The test substance was demonstrated to be non-irritating to skin and eyes and is therefore not to be classified according to the CLP regulation.