Registration Dossier

Toxicological information

Eye irritation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guidelineopen allclose all
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Hostavin TM N 20
- Physical state: white powder

Test animals / tissue source

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

Test system

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

Results and discussion

Results of in vivo studyopen allclose all
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.

Applicant's summary and conclusion

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