Registration Dossier

Administrative data

Description of key information

The given test chemical was not irritating to the skin and eyes of the rabbits.  

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:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary source.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Skin Irritation study was conducted for the given test chemical.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: adult, nulliparous, nonpregnant, female rabbits
- Weight at study initiation: weighing 3.4, 3.6 and 4.0 kg were used in the study
- Housing: Rabbits were individually housed in stainless steel cages
- Diet (e.g. ad libitum): Animals were fed 100-120 g standard diet per animal/day
- Water (e.g. ad libitum): allowed free access to tap water
- Acclimation period: They were quarantined for at least 14 days before use.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 1.5 degrees C
- Humidity (%): 40-70% relative humidity
- Air changes (per hr): 500 lux illumination, 12-15 air exchanges per hour.
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 Hours
Observation period:
7 Days
Number of animals:
Total = 3
Details on study design:
TEST SITE
- Area of exposure: the dorso-lateral area of the trunk
- % coverage: 6 x 6 cm
- Type of wrap if used: hypoallergenic patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): dressings were removed and the exposed skin was carefully washed with water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
- Method of calculation: Dermal irritation was scored for the degree of erythema/eschar formation according to the method of Draize after 1, 24, 48, and 72 hours and 7 days. Erythema/eschar and edema were each scored on a scale of 0-4 (no effect to severe effect). Any serious lesions or toxic effects other than dermal irritation were recorded. The Draize scores at 24, 48 and 72 hours were added. The total of the three scores was divided by three to give the irritation index. This index was calculated sep arately for erythema/eschar formation and edema. Data interpretation was based on the individual indices of the two most sensitive animals.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test chemical was not irritating to the skin.
Interpretation of results:
other: not irritating
Conclusions:
The given test chemical was not irritating to the skin.
Executive summary:

Skin irritation study was performed for the given test chemical as per OECD Guideline 404 (Acute Dermal Irritation / Corrosion) on New Zealand White rabbits. Three healthy, adult, nulliparous, nonpregnant, female rabbits (strain HC:NZW) weighing 3.4, 3.6 and 4.0 kg were used in the study. They were quarantined for at least 14 days before use. During this period, pooled feces specimens were examined for Coccidia oocysts. Rabbits were individually housed in stainless steel cages under standardized conventional conditions (21 +/- 1.5 degrees C, 40-70% relative humidity, 12 hour light/dark cycle, 500 lux illumination, 12-15 air exchanges per hour). They were fed 100-120 g standard diet per animal/day and allowed free access to tap water. The animals were examined one day prior to use. Only animals not exhibiting any alterations to skin or eyes were used. Approximately 24 hours before the test, fur was clipped from the dorso-lateral area of the trunk (6 x 6 cm) of each of the rabbits. Care was taken to avoid abrasion. Pulverized test material (500 mg) was moistened with deionized water and applied to a hypoallergenic patch. An additional patch as moistened only with water. The patches were placed on the opposite dorso-lateral areas of the trunk of each animal. They were held in place with a semiocclusive dressing for 4 hours. The area of exposure was approximately 6 cm2. After 4 hours, dressings were removed and the exposed skin was carefully washed with water. Dermal irritation was scored for the degree of erythema/eschar formation according to the method of Draize after 1, 24, 48, and 72 hours and 7 days. Erythema/eschar and edema were each scored on a scale of 0-4 (no effect to severe effect). Any serious lesions or toxic effects other than dermal irritation were recorded. The Draize scores at 24, 48 and 72 hours were added. The total of the three scores was divided by three to give the irritation index. This index was calculated sep arately for erythema/eschar formation and edema. Data interpretation was based on the individual indices of the two most sensitive animals. All scores were 0. Hence, the given test chemical was not irritating to the skin.  

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:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary source.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Eye irritation study was conducted for the given test chemical.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: healthy, adult, nulliparous, nonpregnant, female rabbits
- Weight at study initiation: weighing 2.9, 3.4 and 3.4 kg were used in the study.
- Housing: Rabbits were individually housed in stainless steel cages
- Diet (e.g. ad libitum): Animals were fed 100-120 g standard diet per animal/day
- Water (e.g. ad libitum): allowed free access to tap water
- Acclimation period: They were quarantined for at least 14 days before use.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 1.5 degrees C
- Humidity (%): 40-70% relative humidity
- Air changes (per hr): 12-15 air exchanges per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle 500 lux illumination
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent negative control
Amount / concentration applied:
39 mg
Duration of treatment / exposure:
24 Hours
Observation period (in vivo):
7 Days
Number of animals or in vitro replicates:
Total = 3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye was rinsed with normal saline 24 hours after treatment
- Time after start of exposure: 24 hours

SCORING SYSTEM: Eye irritation was scored and recorded at 1, 24, 48, and 72 hours and 7 days. The signs of cornea (opacity and area affected), iris (hyperemia, reaction to light), conjunctivae (erythema, chemosis), and discharge were recorded as described by Draize.

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48 h
Score:
1
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
other: Discharge scores
Basis:
mean
Time point:
other: 1 h
Score:
1
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
other: Swelling scores
Basis:
mean
Time point:
other: 1 h
Score:
1
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Interpretation of results:
other: Not Irritating
Conclusions:
The given test chemical was Not Irritating to rabbits' eyes.
Executive summary:

Eye irritation study was conducted for the given test chemical as per OECD Guideline 405 (Acute Eye Irritation / Corrosion) on rabbits. Three healthy, adult, nulliparous, nonpregnant, female rabbits (strain HC:NZW) weighing 2.9, 3.4 and 3.4 kg were used in the study. They were quarantined for at least 14 days before use. During this period, pooled feces specimens were examined for Coccidia oocysts. Rabbits were individually housed in stainless steel cages under standardized conventional conditions (21 +/- 1.5 degrees C, 40-70% relative humidity, 12 hour light/dark cycle, 500 lux illumination, 12-15 air exchanges per hour). They were fed 100-120 g standard diet per animal/day and allowed free access to tap water. The animals were examined one day prior to use. Only animals not exhibiting any alterations to skin or eyes were used. The lower lid was gently pulled away from the eyeball and a volume of 100 microliters of pulverized test material (approximately 39 mg) was placed into the conjunctival sac of one eye of each of the rabbits. The lids were then gently held together for about 1 second. The other eye remained untreated and served as the control. The treated eye was rinsed with normal saline 24 hours after treatment. Eye irritation was scored and recorded at 1, 24, 48, and 72 hours and 7 days. The signs of cornea (opacity and area affected), iris (hyperemia, reaction to light), conjunctivae (erythema, chemosis), and discharge were recorded as described by Draize. Any serious lesions or toxic effects other than ocular were recorded. Examinations of the cornea, iris and aqueous humor were facilitated using optical instruments (e.g. hand slit lamp). To define epithelial dam age, one drop of a 1% fluorescein solution was applied to the corneal surface 24 hours after treatment. The eye was then rinsed with normal saline. The eyes were examined under UV light in a darkened room and under diffuse white illumination according to the method of McDonald and Shadduck. This procedure was repeated later if positive effects were noted. Only effects persisting for more than 24 hours were included in the evaluation. The irritation indices/mean irritation indices were calculated for cornea (opacity), iris, and erythema and swelling (chemosis) of the conjunctivae. The interpretation was based on the individual indices obtained from the two most sensitive animals. Conjunctival redness scores of 1 (some blood vessels definitely hyperemic) were observed at 1 and 24 hours in all rabbits and also at 48 hours in one rabbit. Discharge scores of 1 (slightly increased) were observed in 2 rabbits at 1 hour. Swelling scores of 1 (swelling slightly above normal, including nictitating membrane) were observed in 2 rabbits at 1 hour. All other scores were 0. The given test chemical was Not Irritating to rabbits' eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation

Skin irritation study was performed for the given test chemical as per OECD Guideline 404 (Acute Dermal Irritation / Corrosion) on New Zealand White rabbits. Three healthy, adult, nulliparous, nonpregnant, female rabbits (strain HC:NZW) weighing 3.4, 3.6 and 4.0 kg were used in the study. They were quarantined for at least 14 days before use. During this period, pooled feces specimens were examined for Coccidia oocysts. Rabbits were individually housed in stainless steel cages under standardized conventional conditions (21 +/- 1.5 degrees C, 40-70% relative humidity, 12 hour light/dark cycle, 500 lux illumination, 12-15 air exchanges per hour). They were fed 100-120 g standard diet per animal/day and allowed free access to tap water. The animals were examined one day prior to use. Only animals not exhibiting any alterations to skin or eyes were used. Approximately 24 hours before the test, fur was clipped from the dorso-lateral area of the trunk (6 x 6 cm) of each of the rabbits. Care was taken to avoid abrasion. Pulverized test material (500 mg) was moistened with deionized water and applied to a hypoallergenic patch. An additional patch as moistened only with water. The patches were placed on the opposite dorso-lateral areas of the trunk of each animal. They were held in place with a semiocclusive dressing for 4 hours. The area of exposure was approximately 6 cm2. After 4 hours, dressings were removed and the exposed skin was carefully washed with water. Dermal irritation was scored for the degree of erythema/eschar formation according to the method of Draize after 1, 24, 48, and 72 hours and 7 days. Erythema/eschar and edema were each scored on a scale of 0-4 (no effect to severe effect). Any serious lesions or toxic effects other than dermal irritation were recorded. The Draize scores at 24, 48 and 72 hours were added. The total of the three scores was divided by three to give the irritation index. This index was calculated sep arately for erythema/eschar formation and edema. Data interpretation was based on the individual indices of the two most sensitive animals. All scores were 0. Hence, the given test chemical was not irritating to the skin.  

Eye Irritation

Eye irritation study was conducted for the given test chemical as per OECD Guideline 405 (Acute Eye Irritation / Corrosion) on rabbits. Three healthy, adult, nulliparous, nonpregnant, female rabbits (strain HC:NZW) weighing 2.9, 3.4 and 3.4 kg were used in the study. They were quarantined for at least 14 days before use. During this period, pooled feces specimens were examined for Coccidia oocysts. Rabbits were individually housed in stainless steel cages under standardized conventional conditions (21 +/- 1.5 degrees C, 40-70% relative humidity, 12 hour light/dark cycle, 500 lux illumination, 12-15 air exchanges per hour). They were fed 100-120 g standard diet per animal/day and allowed free access to tap water. The animals were examined one day prior to use. Only animals not exhibiting any alterations to skin or eyes were used. The lower lid was gently pulled away from the eyeball and a volume of 100 microliters of pulverized test material (approximately 39 mg) was placed into the conjunctival sac of one eye of each of the rabbits. The lids were then gently held together for about 1 second. The other eye remained untreated and served as the control. The treated eye was rinsed with normal saline 24 hours after treatment. Eye irritation was scored and recorded at 1, 24, 48, and 72 hours and 7 days. The signs of cornea (opacity and area affected), iris (hyperemia, reaction to light), conjunctivae (erythema, chemosis), and discharge were recorded as described by Draize. Any serious lesions or toxic effects other than ocular were recorded. Examinations of the cornea, iris and aqueous humor were facilitated using optical instruments (e.g. hand slit lamp). To define epithelial dam age, one drop of a 1% fluorescein solution was applied to the corneal surface 24 hours after treatment. The eye was then rinsed with normal saline. The eyes were examined under UV light in a darkened room and under diffuse white illumination according to the method of McDonald and Shadduck. This procedure was repeated later if positive effects were noted. Only effects persisting for more than 24 hours were included in the evaluation. The irritation indices/mean irritation indices were calculated for cornea (opacity), iris, and erythema and swelling (chemosis) of the conjunctivae. The interpretation was based on the individual indices obtained from the two most sensitive animals. Conjunctival redness scores of 1 (some blood vessels definitely hyperemic) were observed at 1 and 24 hours in all rabbits and also at 48 hours in one rabbit. Discharge scores of 1 (slightly increased) were observed in 2 rabbits at 1 hour. Swelling scores of 1 (swelling slightly above normal, including nictitating membrane) were observed in 2 rabbits at 1 hour. All other scores were 0. The given test chemical was Not Irritating to rabbits' eyes.

Justification for classification or non-classification

The given test chemical was not irritating to the skin and eyes of the rabbits. Hence, the given test chemical was not classified for skin and eyes as per CLP criteria.