Registration Dossier

Administrative data

Description of key information

The potential irritant and/or corrosive effects of the test substanceon skin were evaluated in two studies on the skin of New Zealand White rabbits. The material caused very slight edema in one study. Edema resolved within 48h. In the second test, the substance did not cause any irritation on skin. Application of the substance to eyes resulted in iridal and slight conjunctival irritation which resolved within 72h and 7d, respectively. Therefore, the substance is considered to be as non-irritant to skin and eyes.

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:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
1998
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS New Zealand White rabbits
- Source: Myrtle's Rabbitry, Thompson Station, TN
- Age at study initiation: adult
- Weight at study initiation: not mentioned
- Housing: housed individually in suspended stainless steel cages
- Diet (e.g. ad libitum): PMI Certified Rabbit Chow ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 33-35
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: 6.-10.3.2000
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g, 100%
Duration of treatment / exposure:
4h
Observation period:
72h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: /
- Type of wrap if used: elastic wrap was then further secured with adhesive tape around the trunk at the cranial and caudal ends

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gauze moistened with deionized water followed by dry gauze.
- Time after start of exposure: 4h

Dermal Observations
Animals were examined for signs of erythema and edema and the responses scored 1 hour after patch removal and at approximately 24, 48 and 72 hours after patch application according to the Macroscopic Dermal Grading System which is based on Draize.

Clinical Observations
Any unusual observations and/or mortality were recorded. General health/mortality checks were performed twice daily (in the morning and in the
afternoon).

Body Weights
Individual body weights were obtained for each animal priorto dosing on day 0 and prior to euthanasia.

Gross Necropsy
Each animal was euthanized by an intravenous injection of sodium pentobarbital following its final scoring interval. Gross necropsy examinations were not required for these animals.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4

Table 1: Mean Irritation Scores in Individual Animals

Animal No.

Erythema

Edema

R2101/M

R2102/M

R2103/M

0.33

0.00

0.33

0.00

0.00

0.00

Irritation Rating

Nonirritant

Nonirritant

Interpretation of results:
GHS criteria not met
Executive summary:

The potential irritant and/or corrosive effects of the test substance were evaluated on the skin of New Zealand White rabbits. Each of three rabbits received a 0.50 g dose of the test article as a single dermal application. The test article was moistened with deionized water to enhance test article contact with the skin. The dose was held in contact with the skin under a semi-occlusive binder for an exposure period of four hours. Following the exposure period, the binder was removed and the remaining test article was wiped from the skin using gauze moistened with deionized water followed by dry gauze. Test sites were subsequently examined and scored for dermal irritation for up to 72 hours following patch application. Exposure to the test article produced very slight erythema on 3/3 test sites at the 1 -hour scoring interval. The dermal irritation resolved completely on all test sites by the 48-hour scoring interval.

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:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS New Zealand White rabbits
- Source: Myrtle's Rabbitry, Thompson Station, TN
- Age at study initiation: adult
- Weight at study initiation: not mentioned
- Housing: housed individually in suspended stainless steel cages
- Diet (e.g. ad libitum): PMI Certified Rabbit Chow ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 33-35
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: 7.-14..3.2000
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.0510 g
(0.1 mL weight equivalent)
Duration of treatment / exposure:
The test article was instilled into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eye. Following instillation, the eyelids were gently held together for approximately one second in order to limit test article loss and the animal was returned to its cage. The eyes were macroscopically examined with the aid of an auxiliary light source for signs of irritation at 1, 24, 48 and 72 hours and up to 7 days after dosing
Observation period (in vivo):
7d
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- no removal

SCORING SYSTEM: Draize system

TOOL USED TO ASSESS SCORE: fluorescein

The test article was instilled into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eye. Following instillation, the eyelids were gently held together for approximately one second in order to limit test article loss and the animal was returned to its cage. The contralateral eye remained untreated to serve as a control.

Ocular Observations
The eyes were macroscopically examined with the aid of an auxiliary light source for signs of irritation at 1, 24, 48 and 72 hours and up to 7 days after dosing according to the Ocular Grading System which is based on Draize. Following macroscopic observations at the 24-hour scoring interval, the fluorescein examination procedure was repeated on all test and control eyes and any residual test article was gently rinsed from the eye at this time (if possible) using physiological saline.

Clinical Observations
Any unusual observations and/or mortality were recorded. General health/mortality checks were performed twice daily (in the morning and in the
afternoon).

Body Weights
Individual body weights were obtained for each animal prior to dosing on day 0 and prior to euthanasia.

Scheduled Euthanasia
Each animal was euthanized by an intravenous injection of sodium pentobarbital following its final observation interval. Gross necropsy examinations were not required for these animals.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.65
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.45
Max. score:
3
Reversibility:
fully reversible
Irritant / corrosive response data:
Exposure to the test article produced iritis in 1/3 test eyes at the 1-hour scoring interval. The iridal irritation resolved completely in the affected test eye by the 48-hour scoring interval. Conjunctivitis (redness, swelling and discharge) was noted in 3/3 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in all test eyes by study day 7. No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

Table 1: Mean irritation scores in individual animals

Animal No.

Corneal Opacity

Iris Lesion

Conjunctival Redness

Conjunctival Edema

R2082/M

R2084/M

R2097/M

0.00

0.00

0.00

0.33

0.00

0.00

0.67

0.67

0.33

1.00

0.33

0.67

Irritation Rating

Nonirritant

Nonirrtant

Nonirritant

Nonirritant

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the EEC labeling criteria, the test substance is classified as a nonirritant to the ocular tissue of the rabbit for corneal opscity, iritis, conjunctival redness and conjunctival edema.
Executive summary:

The potential irritant and/or corrosive effects were evaluated on the eyes of New Zealand White rabbits. Each of three rabbits received a 0.0510 g (0.1 mL weight equivalent) dose of the test article in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 7 days following dosing. Exposure to the test article produced iritis in 1/3 test eyes at the 1-hour scoring interval. The iridal irritation resolved completely in the affected test eye by the 48-hour scoring interval. Conjunctivitis (redness, swelling and discharge) was noted in 3/3 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in all test eyes by study day 7.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Dermal irritation

The potential irritant and/or corrosive effects of the test substance were evaluated in two studies on the skin of New Zealand White rabbits. In the first study, each of three rabbits received a 0.50 g dose of the test article as a single dermal application. The test article was moistened with deionized water to enhance test article contact with the skin. The dose was held in contact with the skin under a semi-occlusive binder for an exposure period of four hours. Following the exposure period, the binder was removed and the remaining test article was wiped from the skin using gauze moistened with deionized water followed by dry gauze. Test sites were subsequently examined and scored for dermal irritation for up to 72 hours following patch application. Exposure to the test article produced very slight erythema on 3/3 test sites at the 1h scoring interval. The dermal irritation resolved completely on all test sites by the 48-hour scoring interval. In a second study, three rabbits received 0.5 g of the test substance as a single dermal application. The test article was moistened with water and held in contact with skin for 4h. After exposure period, test sites were examined and scored for dermal irritation for up to 72h. Application of the substance resulted in no dermal irritation.

 

Ocular Irritation

The potential irritant and/or corrosive effects of the test material were evaluated on the eyes of New Zealand White rabbits. In the first study, each of three rabbits received a 0.0510 g (0.1 ml weight equivalent) dose of the test article in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 7 days following dosing. Exposure to the test article produced iritis in 1/3 test eyes at the 1-hour scoring interval. The iridal irritation resolved completely in the affected test eye by the 48-hour scoring interval. Conjunctivitis (redness, swelling and discharge) was noted in 3/3 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in all test eyes by study day 7. In the second study, each of three rabbits received a 0.058 g (0.1 ml weight equivalent) dose of the test article in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 7 days following dosing. Exposure to the test article produced slight conjunctival irritation in all three animals. All treated eyes had returned to a normal appearance by 72h after treatment.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008.