Registration Dossier

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Administrative data

Description of key information

Skin Irritation:
The substance is not a skin irritant, rabbit (male), OECD 404, EU Method B.4, EPA OPPTS 870.2500 and JMAFF Guidelines, Huygevoort (2006)
Eye Irritation:
The substance is not an eye irritant, rabbit (male), OECD 405, EU Method B.5, EPA OPPTS 870.2400 and JMAFF Guidelines, Huygevoort (2006)

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:
19 October 2006 - 13 December 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Guidelines (2000)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: at least 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: animals were housed individually in labelled cages with perforated floors
- Diet: ca. 100 g per day of pelleted diet for rabbits (K-H from SNIFF® Spezialdiäten GmbH, Soets, Germany). Hay was provided at least three times a week.
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 - 23.2 °C
- Humidity (%): 42 - 69 %
- Air changes (per hr): ca. 15 air changes per day
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Type of coverage:
semiocclusive
Vehicle:
other: The powdery test substance was moistened with 0.5 mL water (Milli-U)
Controls:
no
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
72 hours
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: ca. 24 hours before treatment, the dorsal fur was clipped, exposing an area of ca 150 cm². To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.
- Coverage: each animals was treated by dermal application of 0.5 g of test material that had been moistened with 0.5 mL of water and applied to the skin of one flank.
- Type of wrap if used: the test material was covered with a metalline patch of 2 x 3 cm. The patch was mounted on Micropore tape which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): four hours after application, the dressing was removed and the skin cleaned of residual test material with tap water.

SCORING SYSTEM: skin reaction were scored using the Draize scoring system.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Max. score:
1
Remarks on result:
other: Max. duration: 24 d; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Max. score:
0
Remarks on result:
other: Max. duration: d; Max. value at end of observation period: 0 (related to all animals)
Irritant / corrosive response data:
IRRITATION
Four hours exposure to 0.5 g of test material resulted in very slight erythema in the treated skin-area of one rabbit. The skin irritation had resolved within 24 hours after exposure. No skin irritation was caused by the test material in the other two animals.

CORROSION
There was no evidence of a corrosive effect on the skin.

Other effects:
COLOURATION/ REMNANTS
No staining of the treated skin by the test material was observed and no test material remnants were seen.

TOXICITY/ MORTALITY
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study the test material was found not to be a skin irritant.
Executive summary:

The potential of the test material to cause skin irritation was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 404, EU Method B.4, EPA OPPTS 870.2500 and JMAFF Guidelines.

During the study three male rabbits were exposed to 0.5 g test material, moistened with water by application onto clipped skin for 4 hours using a semi-occulsive dressing. Skin reactions were assessed 1, 24, 48 amd 72 hours after exposure.

Exposure to the test material resulted in very slight erythema in the treated skin area of one rabbit, which resolved within 24 hours after exposure. No skin irritation effects were seen in the other two animals.

Based on these results, the test material was concluded not to be a skin irritant.

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:
23 October 2006 - 13 December 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Guidelines (2000)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: at least 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: animals were housed individually in labelled cages with perforated floors
- Diet: ca. 100 g per day of pelleted diet for rabbits (K-H from SNIFF® Spezialdiäten GmbH, Soets, Germany). Hay was provided at least three times a week.
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9 - 22.1 °C
- Humidity (%): 43 - 69 %
- Air changes (per hr): ca. 15 air changes per day
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): on average, animals were treated by instillation of 37.1 mg (range 36.8 - 37.2 mg) test material (a volume of ca. 0.1 mL), in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for ca. 1 second to prevent loss of the test material. The other eye remained untreated and served as the control.


Duration of treatment / exposure:
72 hours
Observation period (in vivo):
The eys of each animal were examined 1, 24, 48 amd 72 hours after instillation of the test material.
Number of animals or in vitro replicates:
3 males
Details on study design:
SCORING SYSTEM: The irritation reactions were scored using the Draize System.

TOOL USED TO ASSESS SCORE: Immediately after the 24-hour observation, a solution of 2% fluorescein in water was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24h
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 h
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
IRRITATION
Irritation of the cornea was noted, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals.
No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorecein, 24 hours after test material instillation revealed no corneal damage.

CORROSION
There was no evidence of ocular corrosion.

Other effects:
COLOURATION/ REMNANTS
No staining of (peri) ocular tissues by the test material was observed. Remnants of the test material were present in the eye on Day 1.

TOXICITY/ MORTALITY
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
not classified
Remarks:
Migrated information not classified Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study the test material was not found to be irritating to the eyes.
Executive summary:

The potential of the test material to cause eye irritation was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 405, EU Method B.5, EPA OPPTS 870.2400 and JMAFF Guidelines (2000).

During the study single samples of test material (ca. 0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

Instillation of the test material resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals.

Remnants of the test material were present in the eye on Day 1.

Based on the results of this study, the test material is not considered to be an eye irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In the key study, the potential of the test material to cause skin irritation was investigated under GLP conditions and in accordance with the standardised guidelines OECD 404, EU Method B.4, EPA OPPTS 870.2500 and JMAFF Guidelines.

During the study three male rabbits were exposed to 0.5 g test material, moistened with water by application onto clipped skin for 4 hours using a semi-occulsive dressing. Skin reactions were assessed 1, 24, 48 amd 72 hours after exposure.

Exposure to the test material resulted in very slight erythema in the treated skin area of one rabbit, which resolved within 24 hours after exposure. No skin irritation effects were seen in the other two animals.

Based on these results, the test material was concluded not to be a skin irritant.

Supporting information is available in the form of an in vivo study which was conducted in accordance with the standardised guideline OECD 404.

During the study four rabbits were exposed to 0.5 g test material emulsified with Tween-80 by application onto clipped skin for 4 hours using a semi-occulsive dressing. Skin reactions were assessed 24, 48 amd 72 hours after exposure.

No erythema ot edema or any other sig of irritation was observed in the skin of any of the rabbits at any observation point during the three days after patch removal. Therefore, the study was terminated at this time and the maximum primary irritation index of the test material was calculated to be 0.00.

Based on these results, the test material was concluded not to be a skin irritant.

 

Eye irritation:

In the key study, the potential of the test material to cause eye irritation was investigated under GLP conditions and in accordance with the standardised guidelines OECD 405, EU Method B.5, EPA OPPTS 870.2400 and JMAFF Guidelines (2000).

During the study single samples of test material (ca. 0.1 mL) were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

Instillation of the test material resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals.

Remnants of the test material were present in the eye on Day 1.

Based on the results of this study, the test material is not considered to be an eye irritant.

Supporting information is available in the form of an in vivo study which was conducted in accordance with the standardised guideline OECD 405.

During the study single samples of test material (0.1 g) were instilled into one eye of each of four New Zealand White rabbits. Observations were made 1, 24, 48 and 72 hours after instillation and also on days 4 and 5 following instillation.

Observation results of eye irritation after the application comprised diffuse crimson colour, obvious chemosis on conjunctiva coupled with a little discharge. No abnormalities of the cornea or iris were detected. All effects were fully reversible within 4 days after treatment in three animals, and by day 5 in the remianing animal.

Under the conditions of the study the test material was not found to meet the classification criteria as irritating to eye according to the criteria on EU Regulation (EC) 1272/2008.


Justification for classification or non-classification

The substance does not fulfil the classification criteria for classification as a skin or eye irritant according to European Regulation (EC) No 1272/2008.

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