Registration Dossier

Administrative data

Description of key information

The test substance is not irritating to skin (LPT, 2013) or eyes (LPT, 2013).

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:
2013-01-28 to 2013-02-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study; GLP study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
1998
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
TEST ANIMALS: 
- Source: LPT, Laboratory of Pharmacology and Toxicology, Löhndorf (Germany)
- Sex: female
- Age: approx. 5.5 - 10.5 months
- Weight at study initiation: 2.9 kg to 3.6 kg
- Housing: single
- Diet: ad libitum, ssniff K-H (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water: ad libitum, tap water
- Acclimatisation period: at least 20 days
- Controls: untreated skin surrounding the application area
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3 °C
- Humidity (%): 30% - 70%
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 ml test item/patch and animal
Duration of treatment / exposure:
4 hour(s)
Observation period:
Postexposure period: 72 hours (Because no effects have been observed the period of observation is not 14 days but 72 hours.)
Number of animals:
3
Details on study design:
ADMINISTRATION/EXPOSURE
- Preparation of test substance: unchanged
- Area of exposure: dorsal area of trunk, shaved 24 hours in advance,  approx. 6 cm2
- Concentration: 0.5 mL of the test item was applied to the test site (area: approx. 6 cm2).
- Occlusion: gauze patch held in place by semi-occlusive non-irritating  tape dressing
- Washing: at the end of the exposure time no residual test item had to be removed.
- Inital test: As there was no evidence of the test item producing severe irritancy or corrosion by the test item, a single patch was applied to one
animal for 4 hours.
- Confirmatory test: As no corrosive or severe irritant effects were observed in the initial test, 2 further animals were employed 24 hours after start
of the initial test.
EXAMINATIONS
- Examination time points: 60 minutes, 24, 48, 72 hours,
- Scoring system: Draize (0-4 possible scores each for erythema/eschar  and for edema)
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
AVERAGE SCORE
- Erythema: 0
- Edema: 0
Other effects:
no other effects

Findings                                Examination                  Skin irritation scores

of the skin                            schedule                      

animal no.

1             2            3

E/Oe          E/Oe        E/Oe

          500 mg substance/patch/animal

 

erythema and

eschar formations/                           before dosing          0/0           0/0          0/0

oedema formation

time after removal

of the patch

(4-hour exposure)

60 min                        0/0            0/0          0/0

24 hours                          0/0            0/0          0/0

48 hours                          0/0           0/0          0/0

72 hours                      0/0            0/0          0/0

 

0   no pathological findings    

E   erythema and eschar formations 

Oe  oedema

Conclusions:
Under the present test conditions, none of the three male rabbits exposed for 4 hours to 500 mg test substance/patch (semi-occlusive conditions) showed any skin reaction. There were no systemic intolerance reactions. Therefore, the test item was non-irritating to skin, hence no labelling is required.
Executive summary:

The purpose of this study was to examine the test item for acute dermal irritation/corrosion properties in rabbits (patch test), according to OECD guideline 404, EC method B.4.and OCSPP guideline 870.2500.

Under the present test conditions, none of the three male rabbits exposed for 4 hours to 500 mg test substance/patch (semi-occlusive conditions) showed any skin reaction. There were no systemic intolerance reactions. Therefore, the test item was non-irritating to skin, hence no labelling is required.

 

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:
2013-01-28 to 2013-02-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study; GLP study without deviation
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
1998
GLP compliance:
yes
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: 
- Source: LPT, Laboratory of Pharmacology and Toxicology, Löhndorf (Germany)
- Sex: female
- Age: approx. 4.5 to 5.5 months
- Weight at study initiation: 2.2 kg up to 2.7 kg
- Housing: single
- Diet: ad libitum, ssniff K-H (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water: ad libitum, tap water
- Acclimatisation period: at least 20 days
- Controls: identical animal, second eye
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3 °C
- Humidity (%): 30% - 70%
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Vehicle:
unchanged (no vehicle)
Controls:
other: identical animal, left eye
Amount / concentration applied:
Amount: 0.1 mL of the test item was administered per eye

Duration of treatment / exposure:
Single instillation into the conjunctival sac of the right eye, test item was not rinsed
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 female rabbits
Details on study design:
ADMINISTRATION: The test was performed initially using one animal. As no corrosive or severe irritant effects were observed in this animal, 2 further
animals were employed 24 hours after start of the initial test.
0.1 mL of the test item was administered per eye and tested in three animals.
The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were
then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.
REMOVAL OF TEST SUBSTANCE
- Washing: test item was not rinsed
TOOL USED TO ASSESS SCORE: eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48 and 72 hours after the administration. The eye reactions were observed and registered.
At 24 hours after the administration, the eyes were treated additionally with fluorescein and examined.
SCORING SYSTEM: Draize scale
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
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
AVERAGE SCORE
- Cornea: 0
- Iris: 0
- Conjunctivae (Redness): 0
- Conjunctivae (Chemosis): 0
Other effects:
no other effects

Acute eye irritation/corrosion test of test item

Examination of the treated eye

Time after

administration

C O R N E A

I R I S

C O N J U N C T I V A E

 

Opacity

 

Redness#

Chemosis##

 

A n i m a l n o. : 1 / 2 / 3

 

 

 

 

 

right eye: 100 ml test item

 

 

 

 

 

before dosing

0/0/0

0/0/0

0/0/0

0/0/0

 

 

 

 

 

1 hour

0/0/0

0/0/0

0/0/0

0/0/0

 

 

 

 

 

24 hours

0/0/0

0/0/0

0/0/0

0/0/0

 

 

 

 

 

48 hours

0/0/0

0/0/0

0/0/0

0/0/0

 

 

 

 

 

72 hours

0/0/0

0/0/0

0/0/0

0/0/0

 

 

 

 

 

Conclusions:
The test item was n o n - i r r i t a t i n g to eyes, hence, no labelling is required.
Executive summary:

The purpose of this study was to obtain information on the influence of the test substance on rabbit eyes (irritation/corrosion test), according to OECD guideline 405, EC method B.5. and OCSPP guideline 870.2400. Under the present test conditions a single administration of the test item per animal into the conjunctival sac of the right eye of three rabbits caused following effect:

Conjunctival redness, corneaeandirises were not affected by instillation of the test item. There were no systemic intolerance reactions. Therefore, according to the EC Regulatiom 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures, the test substance is non-irritating to eyes, hence, no labelling is required.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Only one study available.

Justification for classification or non-classification

Based on the assessment of two animal studies (skin and eye irritating) and according to criteria of EC Directive 67/548/EEC and EC Regulation 1272/2008 the test item is not irritating to skin and eyes.