Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
2000-05-09 - 2000-06-06
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(1992-07-17)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
(1992-12-29)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
(August 1998)
Deviations:
no
Qualifier:
according to
Guideline:
other: EEC Directive 92/69/EEC (31 July 1992), Annex V, Test B 5 (dated 29 December 1992) and EEC Directive 93/21/EEC, 27 April 1993
Deviations:
no
Qualifier:
according to
Guideline:
other: Gefahrstoff-Verordnung (GefStoffV) of 29 September 1994 (BGBL 1, p. 2557)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): ATEHC, CAS-NO: 144-15-0
- Physical state: liquid
- Expiration date of the lot/batch: 1 November 2000
- Storage condition of test material: at room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 3.31, 3.59 and 5.22 kg
- Housing: Before the animals arrived, the study room and cages were cleaned and disinfected. During the study, the room and cages were cleaned at regular intervals. The rabbits were kept individually in a battery of cages with a cage size of 50 x 45 x 40 cm (L x B x H), equipped with a paper disposal system.
- Diet (e.g. ad libitum): Pelleted breeding diet, offered ad libitum.
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking nipples.
- Acclimation period: more than 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): between 30 and 70 %
- Air changes (per hr): 16 times per hour and filtered adequately
- Photoperiod (hrs dark / hrs light): Artificial light was set to give a cycle of 12 hours light and 12 hours dark with light on at 7.00 a.m.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test substance
Duration of treatment / exposure:
no information given
Observation period (in vivo):
up to 72h after the end of exposure
Number of animals or in vitro replicates:
3 animals: 1 female, 2 male
Details on study design:
The liquid test substance was used undiluted. One of the animals (rabbit no. 1) was treated in advance in order to assess ocular reactions to the test substance. The animal was treated with 0.1 mL of the test item, which was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about 1 sec in order to limit loss of the test item. The untreated right eye served as control.
Since there was no remarkable response to the instillation of the test substance, the further two animals were treated subsequently in the same manner.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2 and #3
Time point:
other: 1h, 24h, 48h and 72h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: #1, #2 and #3
Time point:
other: 1h, 24h, 48h and 72h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: 1h, 24h and 48h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: 72h
Score:
0
Max. score:
1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: #2 and #3
Time point:
other: 1h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: #2 and #3
Time point:
other: 24h, 48h and 72h
Score:
0
Max. score:
1
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
animal: #1, #2 and #3
Time point:
other: 1h, 24h, 48h and 72h
Score:
0
Max. score:
0
Irritant / corrosive response data:
The mean grades of ocular reactions at 24, 48 and 72 h after instillation were lower than the value classified as irritant by the EEC Directive 93/21/EEC of 27 April 1993 and the Gefahrstoffverordnung (GefStoffV) of 29 September 1994 (BGB1. I, p. 2557). When administered to the eye, the test substance may be classified as "non-irritant".
Other effects:
Clinical Observations: Slight redness of the conjunctivae and slight discharge were observed in all animals 1 h after instillation. Slight redness was still apparent up to 48 h after instillation in one animal.
No other toxic effects than slight ocular irritation were observed.

Any other information on results incl. tables

Grades for ocular lesions (as stipulated by OECD 405)

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

 Iris  Grade
 Normal
 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  Grade
 Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)  
 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 nictitating membranes Grade 
 No swelling  0
 Any swelling above normal (including nictitating 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

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The test substance can be regarded as non irritant according to the results of the study.
Executive summary:

The potential toxicity of acetyltri-2 -ethylhexylcitrate (ATEHC) was assessed in an acute eye irritation/corrosion test on 3 albino rabbits according to OECD 405 and EU method B.5 in compliance with GLP (2000). In each animal, 0.1 mL of the test substance was introduced into the conjunctival sac of the left eye, the untreated right eye served as control. Both eyes were examined at 1, 24, 48 and 72 h post applicationem. The following results were obtained: Slight redness of the conjunctivae and slight discharge were observed in all animals 1 h after instillation. Slight redness was still apparent up to 48 h after instillation in one animal. The observed findings were fully reversible within 72 h p.a. - no other toxic effects than slight ocular irritation were observed.

It can be assumed that the same applies to tributyl citrate (CAS 77-94-1) as it is a near analogue to the test substance acetyltri-2 -ethylhexylcitrate' (ATEHC).