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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:
13. September 2010 - 28. September 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study under GLP, according to international guidelines and with full documentation

Data source

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

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- The analysis was performed for the reference sample "Sample 2010" as defined in Section 1.4
- Batch No : Ref.Nr 10013593
- Expiry date: 03 January 2011
- Storage : +6°C ± 3°C, in darkness, under inert gas.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste –F40260 Linxe)
- Age at study initiation: 11 or 15 weeks old
- Weight at study initiation: between 1.93 kg and 3.53 kg
- Housing: individual box

- Diet (e.g. ad libitum), Water (e.g. ad libitum): Drinking water (tap-water from public distribution system) and foodstuff (SDS - C15) were supplied freely.
- Acclimation period: a minimal 5-day acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (07.00 to 19.00) and twelve hours darkness

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: One eye was treated and the other eye served as a control.
Amount / concentration applied:
amount: 0.1 mL
Observation period (in vivo):
Ocular examinations were performed on both right and left eyes 1 hour, 24, 48 and 72 hours following treatment.
NOTE: As persistent reactions were noted at 72 hours post-dose, additional observations have been carried out from day 4 daily for up to 9 days in order to determine the reversible character of the lesions observed.
Number of animals or in vitro replicates:
3 males
Details on study design:
Eye examinations were carried out using the scale of lesion scores according to OECD 405.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: between days 7 and 9
Remarks on result:
other: a moderate redness noted 1 hour after the test item instillation
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h
Score:
1.8
Max. score:
4
Reversibility:
fully reversible within: between days 7 and 8
Remarks on result:
other: a moderate to important chemosis noted 1 hour after the test item instillation
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: one day
Remarks on result:
other: a congestion, noted 1 hour after the test item instillation in two animals
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Time point:
other: mean of 24h, 48h, 72h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 2 days
Remarks on result:
other: a moderate corneal opacity

Any other information on results incl. tables

INDIVIDUAL AND MEAN SCORES OF CONJUNCTIVAE, IRIS AND CORNEA

Animal n° Time after treatment Conjunctivae Iris Cornea
Chemosis (A) Redness (C ) Lesion (D) Opacity (E )
A0356 24 hours 2 2 0 2
48 hours 1 2 0 0
72 hours 1 2 0 0
Total 4 6 0 2
Mean 1.3 2 0 0.7
A0374 24 hours 2 2 0 2
48 hours 2 2 0 0
72 hours 2 1 0 0
Total 6 5 0 2
Mean 2 1.7 0 0.7
A0375 24 hours 2 3 0 2
48 hours 2 2 0 0
72 hours 2 2 0 0
Total 6 7 0 2
Mean 2 2.3 0 0.7
Classificationin accordance with the European regulation According to the calculated means, the test item has to be classified R36 "irritating to eyes".
Classificationin accordance with the GHS regulation According to the calculated means, the test item has to be classified in category 2 "irritating to eyes" with the hazard statement H319 "causes serious eye irritation".

TOTAL AND INDIVIDUAL SCORES OF OCULAR IRRITATION

Animal No: A0356

Observation time Conjunctivae Iris Cornea Individual irritation index
  A B C (A+B+C)x2 D Dx5 E F ExFx5
        X=   Y=     Z= X+Y+Z=
1 hour (D0) 2 3 2 14 1 5 0 0 0 19
24 hours (D1) 2 0 2 8 0 0 2 1 10 18
48 hours (D2) 1 0 2 6 0 0 0 0 0 6
72 hours (D3) 1 0 2 6 0 0 0 0 0 6
Day 4 (D4) 1 0 2 6 0 0 0 0 0 6
Day 5 (D5) 1 0 2 6 0 0 0 0 0 6
Day 6 (D6) 1 0 2 6 0 0 0 0 0 6
Day 7 (D7) 0 0 2 4 0 0 0 0 0 4
Day 8 (D8) 0 0 1 2 0 0 0 0 0 2
Day 9 (D9) 0 0 0 0 0 0 0 0 0 0

Animal No: A0374

Observation time Conjunctivae Iris Cornea Individual irritation index
  A B C (A+B+C)x2 D Dx5 E F ExFx5
        X=   Y=     Z= X+Y+Z=
1 hour (D0) 3 3 2 16 1 5 0 0 0 21
24 hours (D1) 2 0 2 8 0 0 2 1 10 18
48 hours (D2) 2 0 2 8 0 0 0 0 0 8
72 hours (D3) 2 0 1 6 0 0 0 0 0 6
Day 4 (D4) 1 0 1 4 0 0 0 0 0 4
Day 7 (D7) 1 0 0 2 0 0 0 0 0 2
Day 8 (D8) 0 0 0 0 0 0 0 0 0 0

Animal No: A0375

Observation time Conjunctivae Iris Cornea Individual irritation index
  A B C (A+B+C)x2 D Dx5 E F ExFx5
        X=   Y=     Z= X+Y+Z=
1 hour (D0) 3 3 2 16 0 0 0 0 0 16
24 hours (D1) 2 0 3 10 0 0 2 1 10 20
48 hours (D2) 2 0 2 8 0 0 0 0 0 8
72 hours (D3) 2 0 2 8 0 0 0 0 0 8
Day 4 (D4) 1 0 1 4 0 0 0 0 0 4
Day 7 (D7) 1 0 0 2 0 0 0 0 0 2
Day 8 (D8) 0 0 0 0 0 0 0 0 0 0

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Remarks:
Migrated information
Conclusions:
In conclusion, the results obtained, under these experimental conditions, enable to conclude that the test item reaction mass of 2.2’-oxybisbutane (DSBE), DIPE, SBA and 2-methylpropan-2-ol (TBA) has to be classified R36 “irritating to eyes” according to the criteria for the classification,
packaging and labelling of dangerous substances in compliance with the E.E.C. Directive n° 67/548, 2001/59 and 99/45. The item is to be
characterised by the symbol “Xi” and the warning label “irritant”. In accordance with the Regulation EC No. 1272/2008 on classification, labelling
and packaging of substances and mixtures, the test item has to be classified in category 2 “Irritating to eyes”. The signal word “Warning” and
hazard statement H319 “Causes serious eye irritation” are required.
Executive summary:

Acute eye irritation was assessed for reaction mass of 2.2’-oxybisbutane (DSBE), DIPE, SBA and 2 -methylpropan-2 -ol (TBA) according to OECD guideline No 405. The test item was instilled as supplied, into the eye of 3 New Zealand rabbits at the dose of 0.1 mL. The experimental protocol was established on the basis of the official method as defined in the OECD guideline No 405 dated April 24th, 2002 and the test method B.5 of the Council regulation No 440/2008. The ocular reactions observed during the study have been moderate to important and totally reversible in the three animals:

- at the conjunctivae level: a moderate redness noted 1 hour after the test item instillation and totally reversible between days 7 and 9, associated with a moderate to important chemosis noted 1 hour after the test item instillation and totally reversible between days 7 and 8,

- at the iris level: a congestion, noted 1 hour after the test item instillation in two animals, and totally reversible on day 1.

- at the corneal level: a moderate corneal opacity, noted 24 hours after the test item instillation, and totally reversible on day 2.

In conclusion, the results obtained, under these experimental conditions, enable to conclude that the test item reaction mass of 2.2’-oxybisbutane (DSBE), DIPE, SBA and 2-methylpropan-2-ol (TBA) has to be classified R36 “irritating to eyes” according to the criteria for the classification, packaging and labelling of dangerous substances in compliance with the E.E.C. Directive n° 67/548, 2001/59 and 99/45. The item is to be characterised by the symbol “Xi” and the warning label “irritant”.

In accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures, the test item has to be classified in category 2 “Irritating to eyes”. The signal word “Warning” and hazard statement H319 “Causes serious eye irritation” are required.