Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from December 1993 to January 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The test is done following EU Directives Guidelines and under GLP. It also contains the Quality Assurance Statement and the substance is well characterised
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Hexyl cinnamic aldehyde
-Storage conditions: at 4 ºC in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield (UK) Lt., Petersfield, Hampshire
- Age at study initiation: 12 to 13 weeks
- Weight at study initiation: 2.8 to 3.1 Kg
- Housing: they were housed individually in plastic cages with perforated floors
- Diet (e.g. ad libitum): standard laboratory diet SDS Stanrab (P) Rabbit Diet ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx at 19 ºC
- Humidity (%): 30 to 70 %
- Air changes (per hr): approx 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours artificial light

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye of each animal was used as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Unwashed
Observation period (in vivo):
Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation.
Number of animals or in vitro replicates:
A total of three animals were used. One of the animals was treated in advance of the others, to ensure that if severe response was produced, no further animals would be exposed.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing
- Time after start of exposure: not applicable


SCORING SYSTEM:
Cornea

Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity: 0
Scattered or diffuse areas of opacity: 1
Easily discernible translucent areas, details of iris slightly obscured: 2
Nacreous areas, no details of iris visible, size of pupil barely discernible: 3
Opaque cornea, iris not discernible through the opacity: 4

Iris

Normal: 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any 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

Conjunctivae

Redness (refers to the most severe reading of palpebral and bulbar conjunctivae, as compared to the control eye)
Blood vessels normal: 0
Some blood vessels definitely hyperaemic (injected): 1
Diffuse, crimson colour, individual vessels not easily discernible: 2
Diffuse beefy red: 3

Chemosis (lids and/or nictating membranes)
No swelling: 0
Any swelling above normal (includes nictating membranes): 1
Obvious swelling with partial eversion of lids: 2
Swelling with lids about half-closed: 3
Swelling with lids more than half-closed: 4


TOOL USED TO ASSESS SCORE: handheld light

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 2 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 2 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: overall 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effect observed
Irritant / corrosive response data:
See Table 7.3.2/1
Other effects:
There were no signs of toxicity or ill health in any rabbit during the observation period

Any other information on results incl. tables

Table 7.3.2/1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Rabbit number and sex Region of eye 1 h Day after instillation
1 2 3 4 7
2889 male Cornea 0 0 0 0 0 0
Iris 0 0 0 0 0 0
Conjunctiva Redness 2 1 0 0 0 0
Chemosis 2 0 0 0 0 0
2919 male Cornea 0 0 0 0 0 0
Iris 0 0 0 0 0 0
Conjunctiva Redness 2 1 0 0 0 0
Chemosis 1 0 0 0 0 0
2920 male Cornea 0 0 0 0 0 0
Iris 0 0 0 0 0 0
Conjunctiva Redness 2 1 0 0 0 0
Chemosis 2 0 0 0 0 0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, HCA is not classified for eye irritation according to the Annex VI of the CLP Regulation 1272/2008/EC and of the Directive 67/548/EEC.
Executive summary:

In an eye irritation study performed according to the EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion) and in compliance to the GLP, 0.1 mL of undiluted Hexyl cinnamic aldehyde (HCA) was instilled into the conjunctival sac of left eye of 3 male New Zeland White Rabbit. After the instillation the substance was not remained. Animals were then observed for 7 days.

The mean individual score were calculated within 3 scoring times (24, 48 and 72 hrs).

The mean individual scores were 0/0/0 for cornea, iris and chemosis. The slight conjunctivae redness, observed (0.33/033/033) was completely reversible within 2 days.

 

Under the test conditions, HCA is not classified for eye irritation according to the Annex VI of the CLP Regulation 1272/2008/EC and of the Directive 67/548/EEC.

 

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.