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Diss Factsheets

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:
26-OCT-2005 - 04-NOV-2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
-
EC Number:
479-300-2
EC Name:
-
Molecular formula:
unspecified
IUPAC Name:
7,14,25,32-tetraazaundecacyclo[21.13.2.2²,⁵.0³,¹⁹.0⁴,¹⁶.0⁶,¹⁴.0⁸,¹³.0²⁰,³⁷.0²⁴,³².0²⁶,³¹.0³⁴,³⁸]tetraconta-1(36),2(40),3,5(39),6,8(13),9,11,16,18,20,22,24,26(31),27,29,34,37-octadecaene-15,33-dione; 7,14,25,32-tetraazaundecacyclo[21.13.2.2²,⁵.0³,¹⁹.0⁴,¹⁶.0⁶,¹⁴.0⁸,¹³.0²⁰,³⁷.0²⁵,³³.0²⁶,³¹.0³⁴,³⁸]tetraconta-1(36),2(40),3,5(39),6,8(13),9,11,16,18,20,22,26(31),27,29,32,34,37-octadecaene-15,24-dione
Test material form:
solid: nanoform, no surface treatment
Details on test material:
- State of aggregation: solid, powder
- Particle size distribution (TEM): 30.3 nm (D50)
- Mass median aerodynamic diameter (MMAD): not specified
- Geometric standard deviation (GSD): not specified
- Shape of particles: spherical
- Surface area of particles: 16.8 m²/g
- Crystal structure: crystalline
- Coating: no
- Surface properties: not applicable
- Density: 1515 kg/m³ at 20°C
- Moisture content: refer to IUCLID chapter 1
- Residual solvent: refer to IUCLID chapter 1
- Activation: not applicable
- Stabilisation: not applicable
Specific details on test material used for the study:
- Physical state: Solid, black powder
- Analytical purity: > 99%
- Storage condition of test material: Room temperature
- Expiration date of the lot/batch: 18 November 2020
- CAS No. Cis: 55034-81-6 Trans: 55034-79-2

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353 Kisslegg/Germany
- Age at study initiation: 11 to 12 weeks (male), 12 to 14 weeks (females)
- Weight at study initiation: 2085, 2725, 2667 g.
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet : Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 43/05) provided by Provimi Kliba AG, Kaiseraugst.
- Water: Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70 %
- Air changes (per hr): approximately 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark.
- Music was played during the daytime light period.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and served as the reference control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g (per animal) was weighed and applied undiluted

Duration of treatment / exposure:
24 h
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
PREPARATION AND TREATMENT
- The eyes of the animals were examined one day prior to test item administration. Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test.

- On the day of treatment, 0.1 g of test material was placed in the conjunctival sac of the left 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 to prevent loss of test item. The right eye remained untreated and served as the reference control. As it was suspected that the test item might produce irritancy, a single animal (one female) was treated first. As neither a corrosive effect nor a severe irritant effect was observed after the 1- and 24-hour examinations, the test was completed using the two remaining animals.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eyes were rinsed 24 hours after instillation with physiological saline (0.9 % NaCl).
- Time after start of exposure: 24 h

SCORING SYSTEM:
The ocular reaction (i.e. corneal opacity, iridic effects, conjunctivae and chemosis) was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004, at approximately 1, 24, 48 and 72 hours after instillation.

TOOL USED TO ASSESS SCORE: a Varta Cliptrix diagnostic-lamp.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no abnormalities observed
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: No abnormalities observed
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no abnormalities observed.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.56
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity, iris and chemosis were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 0.33 and 0.67 for reddening for all three animals.
 
No abnormal findings were observed in the cornea or iris of any animal at any of the measurement interval. Slight to moderate reddening of the conjunctivae was noted in all animals at the 1-hour reading and persisted as slight reddening in one animal up to the 24-hour reading and in two animals until the 48-hour examination. Slight swelling (chemosis) of the conjunctivae was observed in one animal at the 1-hour reading.
 
Slight to moderate reddening of the sclerae was present in two animals at the 1-hour reading and persisted as slight reddening up to the 24- or 48-hour examination, respectively. Slight ocular discharge was noted in two animals at the 1-hour reading. No abnormal findings were observed in the treated eye of any animal 72 hours after treatment, the end of the observation period for all animals.
 
No staining of the treated eyes produced by the test item was observed. Slight black remnants of the test item were observed in the eye or conjunctival sac of two animals at the 1-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. The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions chosem and based upon the referred classification criteria (Commission Directive 2001/59/EC of August 06, 2001), the test article is considered to be "not irritating" to the rabbit eye.
Executive summary:

The primary eye irritation potential of the test article was investigated in a GLP compliant study according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 g 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 after test item instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 0.33 and 0.67 for reddening and 0.00 for chemosis for all three animals, respectively. The instillation of the test item into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 72 hours after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. Slight black remnants of the test item were observed in the eye or conjunctival sac of two animals at the 1-hour reading. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye.