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Diss Factsheets

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19th January 2010 to 4th February 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of GLP inspection: 15/09/09 Date of Signature on GLP certificate: 26/11/09

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of bis[2,4-bis(2-methylbutan-2-yl)phenyl] 4-(2-methylbutan-2-yl)phenyl phosphite and 2,4-bis(2-methylbutan-2-yl)phenyl bis[4-(2-methylbutan-2-yl)phenyl] phosphite and tris[4-(2-methylbutan-2-yl)phenyl] phosphite.
EC Number:
700-485-5
Cas Number:
939402-02-5
Molecular formula:
Mixture of 4 components, the molecular formulae of which are: C33 H45 O3 P, C38 H55 O3 P, C43 H65 O3 P and C48 H75 O3 P
IUPAC Name:
Reaction mass of bis[2,4-bis(2-methylbutan-2-yl)phenyl] 4-(2-methylbutan-2-yl)phenyl phosphite and 2,4-bis(2-methylbutan-2-yl)phenyl bis[4-(2-methylbutan-2-yl)phenyl] phosphite and tris[4-(2-methylbutan-2-yl)phenyl] phosphite.
Test material form:
liquid: viscous
Details on test material:
Description: clear colourless viscous liquid
Date received: 05 November 2009
Expiry date: 15 June 2010
Storage conditions: approximately 4°C in the dark under nitrogen

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Hillcrest, Belton, Loughborough, UK.
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.26 to 2.92 kg
- Housing: The animals were individually housed in suspended cages.
- Diet: ad libitum - 2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK
- Water: ad libitum - mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

IN-LIFE DATES: From: Day of dosing (Day 0) To: Day of sacrifice - Day 7 :

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): not applicable

VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable
- Concentration (if solution): not applicable
- Lot/batch no. (if required): not applicable
- Purity: not applicable
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
One animal treated initially, then after consideration of the first animal's ocular response, two additional animals were treated.
Details on study design:
PRE-TESTING OBSERVATIONS
- Prior to testing, both eyes of the selected test animals were examined for evidence of ocular irritation or defect. Animals free from ocular damage were used.

METHOD
Initially one animal was treated according to the following procedure, in order to assess the initial pain reaction.
- 0.1ml of the test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eye ball.
- The eye lids were held closed for 1 second before the animal was released.
- The left eye remained untreated and was used as the control.
- Immediately after application of the test material an assessment of the initial pain reaction was made according to the six point pain scale.
- Two additional animals were treated, following the same procedure, after consideration of the ocular response produced in the first animal.
- Observations occurred at the following time points; 1, 24, 48 and 72 hours post application. One treated eye was also examined on day 7.
- Additional Observations: Any other ocular effects or clinical signs of toxicity were also noted.
- Bodyweight: Recorded on day 0 and the end of the observation period.
- Equipment: all examinations were aided by use of a standard opthalmoscope.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not stated in report
- Time after start of exposure: not stated in report.

SCORING SYSTEM: Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC, p 48 to 49) see Table 1.

INTERPRETATIONS OF RESULTS
- The data obtained from the Draize scoring system was subjected to a modified version of the system described by Kay and Calandra (1962) (see Table 2). This was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material.
- If evidence of irreversible ocular damage is noted, the test material will be classified as corrosive to the eye.
- The results were evaluated according to Commission Directive 2001/59/EC.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
Degree of opacity
Basis:
animal: 68822 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: mean
Irritation parameter:
cornea opacity score
Remarks:
Degree of opacity
Basis:
animal: 68842 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: mean
Irritation parameter:
cornea opacity score
Remarks:
Degree of opacity
Basis:
animal: 68843 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: mean
Irritation parameter:
iris score
Basis:
animal: 68822 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: mean
Irritation parameter:
iris score
Basis:
animal: 68842 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: mean
Irritation parameter:
iris score
Basis:
animal: 38843 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
other: mean
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: 68822 Male
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 24hours
Remarks on result:
other: Score of 2 observed at 1 hour - mean value
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: 68842 Male
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score of 2 observed at 1 hour - mean values
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: 68843 Male
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score of 2 observed at 1 hour - mean values
Irritation parameter:
chemosis score
Basis:
animal: 68822 Male
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score of 2 observed at 1 hour - mean values
Irritation parameter:
chemosis score
Basis:
animal: 68842 Male
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score of 2 observed at 1 hour - mean values
Irritation parameter:
chemosis score
Basis:
animal: 68843 Male
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Score of 2 observed at 1 hour - mean values
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48 hour observations. Minimal conjunctival irritation was noted in one treated eye at the 72 hour observation. Two treated eyes appeared normal at the 72 hour observation and the remaining treated eye appeared normal at the 7 day observation.
Other effects:
All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

REET study: following assessment of the data for all endpoints the test material was considered unlikely to have the potential to cause severe ocular irritancy in vivo.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant to the rabbit eye according to a modified Kay and Calandra classification system. The test material did not meet the criteria for classification as an irritant.
Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

-  OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

-  Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

Initial considerations. In the absence of available information indicating that the test material had the potential to produce severe effects in a rabbit eye, a Rabbit Enucleated Eye Test (REET) was performed prior to the in vivo test.

Result. A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Two treated eyes appeared normal at the 72 hour observation and the remaining treated eye appeared normal at the 7 day observation.

Conclusion. The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC.