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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:
2017-01-17 to 2017-04-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
A Bovine Corneal Opacity and Permeability Assay (OECD Guideline number 437) with propyl gallate was performed (Eurofins Munich / BSL Munich Project No. 167610). Based on the results of this test further in vivo testing for assessing acute eye irritation/corrosion is necessary.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2 October 2012
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Source and lot/batch No.of test material: 201601004
- Expiration date of the lot/batch: 01.01.2019
- Purity: 99.93 %
- Storage condition of test material: room temperature

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, 97633, Sulzfeld, Germany
- Age at study initiation: approximately 39 weeks old
- Weight at study initiation: >2 kg
- Housing: ABS-plastic or Noryl rabbit cages, floor 4200 cm2, in an air-conditioned room
- Diet (e.g. ad libitum): free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits, rich in crude fibre
- Water (e.g. ad libitum): free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: adequate acclimatisation period (at least 5 days) under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of test item was applied to the test site
Duration of treatment / exposure:
single treatment, 1h
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
1 rabbit
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye was rinsed with physiological saline 0.9% NaCl 1 hour after the application.
- Time after start of exposure: 1 h

SCORING SYSTEM: Grading System for Ocular Lesion (for details see Table 1 in "Any other information on material and methods")

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not reversible
Remarks:
within 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 hours
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks:
within 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 hours
Irritant / corrosive response data:
After the application into the eye of one male NZW rabbit the test item produced severe irritant occular effects (see Table 2 and Table 3 in "Any other information on results"). Local effects at the treated eye and clinical signs were observed (see Table 3). The inclined position of the head 72 hours after application is considered to be related to the local effects observed at the treated eye and not due to systemic effects of the test item. Before fluorescein examination at the end of the observation period of 72 hours the animal was euthanised for animal welfare reasons. Conjunctival redness, chemosis, hypersecretion, corneal effects and iris lesion were observed and described in Table 2.
Other effects:
- Lesions and clinical observations: after 1 hour slight hypersecretion, after 24 hours moderate hypersecretion, after 48 and 72 hours severe hypersecretion

Any other information on results incl. tables

Table 2: Eye Irritation Scores - Animal No. 1

Observation

Eye Irritation Scores Post-Application After

1(1h)

2(24h)

3(48h)

4(72h)

 

T

C

T

C

T

C

T

C

Average Score (24, 48 and 72 hours)

Redness

0

0

1#

0

1

0

1

0

1.00

Chemosis

2

0

2

0

2

0

2

0

2.00

Iris

n.a.*

0

2**

0

2**

0

2

0

2.00

cornea

3

0

2

0

2

0

2

0

2.00

t= test item; c= control; #= upper rim of conjunctiva and nicticating membrane discoloured white; *=due to complete opacity of the cornea the iris was not visible and thus could not be evaluated; **= no reaction to light

Table 3: Clinical Signs - Animal No. 1 

Time Post-Application Local Findings / Comments Systemic Findings
Test Item Control Test Item
1 h slight hypersecretion nsf nsf
24 h moderate hypersecretion nsf nsf
48 h severe hypersecretion nsf nsf
72 h severe hypersecretion nsf head inclined §

nsf= no specific findings; h= hour(s); §= euthanised for ethical reasons

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In an in vivo acute eye irritation/corrosion study in one rabbit accroding to OECD 405, Propyl gallate produced severely irritant effects, which are not expected to reverse.
Executive summary:

In a primary eye irritation study according to OECD 405, 0.1 g of propyl gallate (99.93 % purity) was applied into the conjunctival sac of one eye of 1 male, 39 weeks old, New Zealand White rabbit. The test substance remained in the eye for 1 hour and was rinsed afterwards with physiological saline (0.9 % NaCl). The animal then was observed for 72 hours. Irritation was scored by the method of Draize after 1, 24, 48 and 72 h.

Under the conditions of the present study, a single ocular application of the test item Propyl gallate to one rabbit at a dose of 0.1 g produced severely irritant effects including conjunctival redness, chemosis, hypersecretion, corneal effects and iris lesion (iridial response grade 2 for 72 hours), which are not expected to reverse.

In this study, propyl gallate is a severe eye irritant based on CLP criteria.