Registration Dossier

Administrative data

Description of key information

Skin:

There is one fully reliable study available on the skin irritancy potential. The test item was tested for its skin irritant properties using 6 Albino Himalayan rabbits. The study was performed equivalent to OECD Guideline 404. 500 mg of the test item were applied to the clipped skin of each rabbit. After 24 h post-application the occlusive covering was removed and the rating for erythema/edema formation was performed 24, 48 and 72 hours after application. With reference to the scores the test item is t classified as "non-irritant" (EU CLP and UN GHS: No Category).

Eye:

There are two reliable studies available on the eye irritancy potential. In the course of both studies the test item was tested for its eye irritant properties in 6 Albino Himalayan rabbits. The studies were performed equivalent to OECD Guideline 405. Effects on conjunctivae (redness and swelling) as well on cornea and iris were observed in all animals. These signs were not reversible within the observation period.

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:
May 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Reference:
Composition 1
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
24 h exposure instead of 4 h
Qualifier:
according to
Guideline:
other: FDA Guideline ยง1500.41 Federal register 38, No. 187, 27.09.1973, p 27019
Deviations:
no
GLP compliance:
no
Remarks:
performed before GLP guidelines
Test material information:
Composition 1
Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG own breed
- Strain: Albino Himalayan, Hoe:HIMK(SPFWiga)
- Weight at study initiation: 1,5-2,5 kg
- Diet: ERKA 8300 (Futtermittelwerk Robert Koch oHG, Hamm/Westf.) ad libitum
- Water ad libitum


ENVIRONMENTAL CONDITIONS
- Housing: single cages

Inlife data: from 20.03. to 23.03.1979
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 g of pure substance (moistened with 0.9 % NaCl solution) was applied
Duration of treatment / exposure:
24 h
Observation period:
24 hours post application
48 hours post application
72 hours post application
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm2
- % coverage: 100 %
The substance was applied over the whole surface of a 2.5 cm2 gauze patch. The patches were fixed with adhesive tape to the prepared skinarea (ca. 18 cm2) and then covered with an occlusive polyethylene foil and further fixed with an elastic bandage (Elastoplast).

SCORING SYSTEM:

Erythema and eschar formation
No erythema.......................................................................................................................0
very slight erythema (barely perceptible)......................................................................1
well-defined erythema......................................................................................................2
moderate to severe erythema..........................................................................................3
severe erythema (beet redness) to slight eschar formation (lesion in depth).........4

Oedema
No oedema...................................................................................................................................0
very slight oedema (barely perceptible)..................................................................................1
slight oedema (edges of area well defined by definite raising)............................................2
moderate oedema (raised approximately 1mm)....................................................................3
severe oedema (raised more than 1mm and extending beyond area of exposure.........4

For each animal the rating for Erythema and eschar formation as well as for Oedema formation was added after 24 and 72 hours. The sum of all values of all animals was calculated and divided by the number of animals and the factor of 4. The classification was conducted according to following evaluation classes:

0.0-0.5..........non irritant
0.6-3.0..........slightly irritant
3.1-5.0..........moderately irritant
5.1-8.0..........severely irritant

Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
4
Remarks on result:
other: no effect
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
4
Remarks on result:
other: no effect
Irritant / corrosive response data:
No erythema/edema observed.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
With reference to the reported scores (mean score of 6 animals (erythema): 0; mean score of 6 animals (edema): 0) and the absence of effects the test item has not to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).
Executive summary:

The test substance is considered as not irritant under the conditions of this Patch-test.

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:
from 1979-03-20 to 1979-03-23
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reference:
Composition 1
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no recovery period
Qualifier:
according to
Guideline:
other: FDA Guideline Ferderal Register 38, No. 187, p. 27019, 27.9.1973
Deviations:
no
GLP compliance:
no
Remarks:
performed before GLP implementation
Test material information:
Composition 1
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG own breed
- Strain: Albino Himalayan, Hoe:HIMK(SPFWiga)
- Weight at study initiation: 1,5-2,5 kg
- Diet: ERKA 8300 (Futtermittelwerk Robert Koch oHG, Hamm/Westf.) ad libitum
- Water ad libitum

ENVIRONMENTAL CONDITIONS
- Housing: single cages

Inlife phase: from 20.03. to 23.03.1979
Vehicle:
physiological saline
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g


VEHICLE
- Amount(s) applied (volume or weight with unit): 4 drops
Duration of treatment / exposure:
24 hours, thereafter, the treated eyes were rinsed with physiol. saline.
Observation period (in vivo):
Observation at 1, 7, 24, 48 and 72 hours after application
Number of animals or in vitro replicates:
6 rabbits
Details on study design:
Left eye of each 6 rabbits was treated with 0.1 g test substance. The right eyes were not treated and used as controls.
24 hours after treatment the treated eyes were rinsed with physiol. saline.
The irritation score were determined at observation times of 1,7,24,48 and 72 hours according to "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (FDA, Austin, Texas, p51, 1975).
At 48 and 72 hours the eyes were also examined after instillation of one drop of 0.01 % fluorescein-sodium solution.

SCORING SYSTEM:

A. CORNEA
Degree of opacity (most dense area used)
No opacity ...................................................................................................................0
Scattered or diffuse areas, details of iris clearly visible........................................1
Easily discernible translucent areas, details of iris slightly obscured................2
Opalescent areas, no details of iris visible , size of pupil barely discernible ....3
Opaque, iris invisible, ulzeration ..............................................................................4

B. Affected area
1 = punctiform up to 1/4 but not 0
2 = more than 1/4 up to 1/2
3 = more than 1/2 up to 3/4
4 = more than 3/4 up t o 4/4

a = A x B x 5 (max 80)

IRIS
Normal ......................................................................................................................... 0
Folds above normal , congestion, swelling, circumcorneal injection (any of all of these or combination of any thereof); iris still reacting to light
(sluggish reaction is positive) ......................... .........................................................1
No reaction to light, haemorrhage, gross destruction (any or all of these) ......2

b = Value x 5 (max. 10)

CONJUNCTIVAE

A. Redness
Blood vessels normal...............................................................................................................0
Blood vessels definitely injected above normal ................................................................. 1
More diffuse, deeper crimson red, individual blood vessels not easily discernible .....2
Diffuse beefy red......................................................................................................................3

B. Chemosi s (refers to palpebral and bulbar conjunctivae)
No swelling .........................................................................................0
Any swelling above normal (includes nictitating membran) ..... 1
Obvious swelling with partial eversion of l i d s ...........................2
Swelling with lids about half closed ................................................3
Swelling with lids half closed to completely closed.......................4

C. Secretion
No secretion......................................................................................................................0
Any secretion above normal...........................................................................................1
Secretion with wetting of palpebra and hair close to palpebra.................................2
Secretion with wetting of palpebra, hair and considerable area around eyes........3

c = (A+B+C) x 2 (max. 20)

For each animal the ratings for cornea (a), iris (b) and conjunctivae (c) were added for the respective time of observation. For each time of observation the mean value was calculated for all animals. The highest determined irritation score for any time of observation was used for classification according following evaluation classes:

0-10..........non irritant
11-25.......slightly irritant
26-56.......moderately irritant
57-110.....severely irritant
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48h, 72h
Max. score:
95
Reversibility:
not specified
Remarks on result:
other: scores of 95 corresponds to "severly irritant"
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
1.3
Max. score:
2
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
1.7
Max. score:
2
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
iris score
Basis:
animal #4
Time point:
other: 24-72 h
Score:
1.3
Max. score:
2
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
iris score
Basis:
animal #5
Time point:
other: 24-72 h
Score:
1.3
Max. score:
2
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
iris score
Basis:
animal #6
Time point:
other: 24-72 h
Score:
0.7
Max. score:
2
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
3.6
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
other: 24-72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
other: 24-72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: mean value over 24-72 h
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
other: 24-72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 h
Remarks on result:
other: mean value over 24-72 h
Irritant / corrosive response data:
The test substance is "severly irritating", the highest obtained scores being 95 for the reading time 48h and 72h.
Furthermore, 4 of 6 animals had a mean cornea score >/= 3. Iris scores of 2 were reached by all test animals except one. There was no reversibility observed within the 72 h recovery period.
Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item induced severe ocular lesions in rabbits which were irreversible within the observation period. Therefore, the substance has to be classified as follows:
- 67/548/EEC: R41
- 1272/2008/EC:Irreversible effects on the eye ( Category 1) / H318
Executive summary:

The test item was tested for its eye irritant properties in 6 Himalyan rabbits.The study was performed equivalent to OECD Guideline 405. Effects on cornea, conjunctivae (redness and swelling) and iris were observed in all animals after application. These signs were not reversible within 72h.

With reference to the reported scores and the irreversibility of the observed effects the test item has to be classified as severely irritant to the eyes according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC):

- 1272/2008/EC:Irreversible effects on the eye ( Category 1) / H318

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Skin:

With reference to the reported results of an in vivo skin irritation study the test substance has not to be classified as irritant to the skin according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

Eye:

With reference the reported scores and the irreversibility of the observed effects the test substance has to be classified as irritant to the eyes (irreversible effects on the eye; Category 1 / H318) according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).