Registration Dossier

Diss Factsheets

Administrative data

Description of key information

There are reliable studies available to assess the potential of the test substance for skin and eye irritation. 
skin irritation
key study, in vivo, rabbit: not irritant (GLP, OECD 404, Clariant, 2008)
key study, in vivo, rabbit: not irritant (non-GLP, similar to OECD 404; BASF SE, 1973)
eye irritation
key study, in vivo, rabbit: not irritant (GLP, OECD 405, BASF SE, 2005)
supporting study, in vivo, rabbit: not irritant (non-GLP, similar to OECD 405; BASF SE, 1973)
supporting study, in vivo, rabbit: not irritant (GLP, OECD 405; Clariant, 2010)

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:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and OECD testing guideline compliant study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
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 Netherlands BV, NL-5961 NM Horst
- Age at study initiation: 13 weeks
- Weight at study initiation: 2292 g – 2451 g
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2008-07-30 To: 2008-08-18
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
0.5g
Duration of treatment / exposure:
4h
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm ( 10 cm x 10 cm shaved , left flank)
- Type of wrap if used: gauze patch, covered with a semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: lukewarm tap water
- Time after start of exposure: 4h

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: At the 1h reading, yellow staining by the test item interfered with erythema scoring.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
0
Reversibility:
other: Not applicable
Irritant / corrosive response data:
The test item caused marked yellow staining of the treated skin at the 1-hour reading in all animals which persisted as light yellow staining up to 72 hours after treatment or test day 10. Due to the marked staining the skin of all the rabbits was not assessable at the 1-hour reading. When assessable, from the 24- hour observation except the staining no skin reactions were observed in all animals up to day 14 post treatment, the end of observation time.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
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:
supporting study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and OECD testing guideline compliant study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1g
Duration of treatment / exposure:
single
Observation period (in vivo):
Throughout 7 days after treatment.
Number of animals or in vitro replicates:
3
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72h
Score:
0.6
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: redness
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
Slight reddening of the conjunctivae was noted from the 1- to 24-hour reading in all animals and persisted in one animal up to the 72-hour reading. Slight swelling (chemosis) was observed in two animals at the 1-hour reading. At the same time, slight reddening of the sclerae and slight to moderate ocular discharge were also observed in all animals. The slight reddening of the sclerae persisted in one animal up to the 24-hour reading.

No corrosion of the cornea was observed at any of the reading times.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining produced by the test item was observed in the treated eyes
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A GLP conform in vivo study was performed to assess the acute dermal irritation or corrosion potential of the test substance in New Zealand White rabbits according to OECD guideline 404 (Clariant, 2008). 0.5 g test item was applied by topical semi-occlusive application to the intact left flank of each of three rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after removal of the dressing.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0).

The test item caused marked yellow staining of the treated skin at the 1-hour reading in all animals which persisted as light yellow staining up to 72 hours after treatment in two animals or test day 10 in the third animal.

Due to the marked yellow staining in all animals 1 hour after treatment, erythema was not assessable at this time point. When assessable, from the 24-hour observation (except the staining) no skin reactions were observed in all animals up to day 14 post treatment (the end of observation time).

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), the test item is considered to be “not irritating” to rabbit skin.

 

An Industrial Hygiene Orientating Investigation study was performed to assess the primary skin irritation potential of the test substance similar to OECD guideline 404 with deviations in a Draize test (BASF SE, 1973). The undiluted test substance was applied to the dorsal skin of twoVienna White rabbits for 20 hours under occlusive dressing. No substance related findings were noted at 24 h and 8 days other than orange remainders of the test substance on the skin. The substance was therefore found to be not irritating to the skin of rabbits.

 

Eye irritation

In a GLP conform study the primary eye irritation potential of the test substance (purity: 92 weight-%) was assessed by a single ocular application of 0.1mL bulk volume (about 26 mg) of the test substance to one eye of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals) (BASF SE, 2005). About one hour after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and on day 7.

Slight or moderate conjunctival redness, slight conjunctival chemosis and slight to moderate discharge were observed in the animals during the course of the study. In addition injected scleral vessels in a circumscribed area or circular were noted in the animals during the observation period.

The ocular reactions were reversible in all animals within 7 days after application at latest. The average score (24 to72 hours) for irritation was calculated to be 0.0 for corneal opacity and for iris, 1.2 for conjunctival redness and 0.2 for chemosis. Mean scores for 24, 48 and 72h per animal for cornea were 1.3, 1.0 and 1.3. Mean scores for 24, 48 and 72h per animal for chemosis were 0, 0.3 and 03.

Considering the described ocular reactions as well as the average score for irritation and applying the CLP criteria, the test item is considered not to be irritating to the eyes.

 

Two additional studies support the results of the study described above.

One is an Industrial Hygiene Orientating Investigation study performed with two Vienna White rabbits in a test protocol similar to OECD guideline 405 with deviations (BASF SE, 1973). A 50 % aqueous solution of the test substance was instilled into the eyes for one hour. Afterwards the test item was washed out and the eyes were observed for a period of 7 days.

Slight conjunctival redness was observed one hour and 24 hours after the beginning of the study. Slight edema was found only one hour after application. All ocular reactions were fully reversible within 8 days after application.

The second supporting study was conducted according to OECD 405. 0.1 g test item was applied into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7 days after test item instillation.

The mean score was calculated separately for each animal across three scoring times (24, 48 and 72 hours after instillation) for corneal opacity, iris light reflex, redness and chemosis of the conjunctivae, respectively. The individual mean scores for corneal opacity and iris light reflex were 0.0 for all three animals. The individual mean scores for the conjunctivae were 1.0, 0.33 and 0.33 for reddening, and 0.0, 0.0 and 0.0 for chemosis, respectively.

The instillation of the test item into the eye resulted in mild to moderate, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, ocular discharge and chemosis. These effects were reversible and were no longer evident 7 days after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or for the iris light reflex of any animals at any of the examinations. No staining of the treated eyes by the test item and no clinical signs were observed.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye. Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), the test item does not have to be classified with respect to eye irritation in rabbits.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin or eye irritation under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EG.

 

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 skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the third time in Directive EC 618/2012.