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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:
1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP standards

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: 40 CFR 163.81-4
Deviations:
yes
Principles of method if other than guideline:
The test material was also instilled in the eye of 3 additional animals and subsequently washed out 30 seconds after treatment with warm water.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Aqueous solution containing ca. 70 wt% TBHP
Tertiary-Butyl Hydroperoxide content 70%

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Marland farms, Hewitt, NJ
- Housing: Indiviual, suspended cages
- Diet (e.g. ad libitum): Wayne Rabbit Ration, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL into the left eye
- Concentration (if solution): undiluted test material (i.e. 70% TBHP)

Duration of treatment / exposure:
First group: 7 days (if positive readings were observed within 7 days, exposure time is 21 days)
Second group: 30 seconds
Observation period (in vivo):
First group: 7 days (21 days if positive readings observed)
Second group: 7 days (21 days if positive readings observed)
Number of animals or in vitro replicates:
First group: 6
Second group: 3
Total: 9 (4 males 5 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with 125 mL of lukewarm water (second group only)
- Time after start of exposure: 30 seconds (second group only)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
mean
Time point:
other: Average over 21 days
Score:
2.3
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Unwashed eye
Irritation parameter:
cornea opacity score
Remarks:
Area
Basis:
mean
Time point:
other: Average over 21 days
Score:
3.72
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Unwashed eye
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Average over 21 days
Score:
0.77
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Unwashed eye
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
other: Average over 21 days
Score:
0.8
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Unwashed eye
Irritation parameter:
conjunctivae score
Remarks:
Chemosis
Basis:
mean
Time point:
other: Average over 21 days
Score:
0.82
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Unwashed eye
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
mean
Time point:
other: Average over 21 days
Score:
1.05
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Unwashed eye
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Time point:
other: Average over 21 days
Score:
2.2
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Washed eye
Irritation parameter:
cornea opacity score
Remarks:
area
Basis:
mean
Time point:
other: Average over 21 days
Score:
3.7
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Washed eye
Irritation parameter:
iris score
Basis:
mean
Time point:
other: Average over 21 days
Score:
0.5
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Washed eye
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: Average over 21 days
Score:
0.7
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Washed eye
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Time point:
other: Average over 21 days
Score:
0.9
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Washed eye
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Time point:
other: Average over 21 days
Score:
1.1
Max. score:
4
Reversibility:
other: see other effects section
Remarks on result:
other: Washed eye
Irritant / corrosive response data:
See table 1 and 2 for detailed results.
Other effects:
First group: All 6 rabbits had mild erythema, mild to marked chemosis and discharge. These changes disappeared in 2 rabbits by day 16 and 3 rabbits by day 21. Rabbit no. 5 was found dead on day 17 of undetermined cause. iritis and corneal opacity was seen in all rabbits. Keratitis, corneal ulcers and keratoconus was also seen. Iritis had cleared in 2 rabbits by day 13 and either persisted in the remainder or the iris could not be visualised due to the corneal opacities that persisted in all six rabbits through 21 days.

Second group: Mild to moderate changes were seen in all six rabbits. These changes cleared in 1 rabbit at 7 days and 1 rabbit by day 21. Iritis and corneal opacities were seen in all three rabbits. In addition, keratoconus, corneal erosions, keratitis and anterior synechia were seen. Iritis had cleared in 1 rabbit by day 7 and persisted through 21 days in the remaining 2. Corneal opacities persisted through 21 days in all three rabbits.

Any other information on results incl. tables

Table 1 Irritation scores for the unwashed eye group.

Animal  
Time Effect 1F 2F 3F 4M 5M 6M Mean
24 hours Cornea Opacity 2 2 2 2 2 2 2.0
  Area 4 4 4 4 4 4 4.0
Iris Value 1 1 1 1 1 1 1.0
Conjunctivae Redness 1 1 1 1 1 1 1.0
  Chemosis 1 2 1 2 3 4 2.2
  Discharge 2 2 2 2 2 2 2.0
48 hours Cornea Opacity 2 2 2 2 2 2 2.0
  Area 4 4 4 4 4 4 4.0
Iris Value 1 1 1 1 1 1 1.0
Conjunctivae Redness 1 1 1 1 1 1 1.0
  Chemosis 1 1 1 2 3 4 2.0
  Discharge 1 2 1 1 2 2 1.5
72 hours Cornea Opacity 3 3 3 2 2 1 2.3
  Area 4 4 4 4 4 4 4.0
Iris Value * * * 1 1 1 1.0
Conjunctivae Redness 1 1 1 1 1 1 1.0
  Chemosis 1 1 1 2 2 2 1.5
  Discharge 1 2 1 1 2 2 1.5
96 hours Cornea Opacity 3 3 3 2 2 1 2.3
  Area 4 4 4 4 4 4 4.0
Iris Value * * * 1 1 1 1.0
Conjunctivae Redness 1 1 1 1 1 1 1.0
  Chemosis 0 1 1 1 1 2 1.0
  Discharge 1 2 1 1 1 2 1.3
7 days Cornea Opacity 2 3 3 3 4 2 2.8
  Area 4 4 4 4 4 4 4.0
Iris Value 1 * * * * 1 1.0
Conjunctivae Redness 1 1 1 1 1 1 1.0
  Chemosis 0 0 0 1 0 1 0.3
  Discharge 1 1 1 2 1 1 1.2
10 days Cornea Opacity 2 3 2 3 3 2 2.5
  Area 4 4 4 4 4 2 3.7
Iris Value 1 * 1 * * 1 1.0
Conjunctivae Redness 1 1 1 1 1 1 1.0
  Chemosis 0 0 0 1 1 1 0.5
  Discharge 1 1 0 2 1 1 1.0
13 days Cornea Opacity 2 2 2 3 3 4 2.7
  Area 4 4 4 4 4 4 4.0
Iris Value 0 1 0 1 * * 0.5
Conjunctivae Redness 1 1 1 1 1 1 1.0
  Chemosis 0 0 0 1 1 1 0.5
  Discharge 1 1 1 1 1 1 1.0
16 days Cornea Opacity 2 2 2 3 d 4 2.2
  Area 4 4 4 4 d 4 3.3
Iris Value 0 1 0 1 d * 0.4
Conjunctivae Redness 0 1 0 1 d 1 0.5
  Chemosis 0 0 0 1 d 0 0.2
  Discharge 0 1 0 1 d 1 0.5
19 days Cornea Opacity 2 2 2 3 d 4 2.2
  Area 4 4 4 4 d 4 3.3
Iris Value 0 1 0 1 d * 0.4
Conjunctivae Redness 0 0 1 1 d 1 0.5
  Chemosis 0 0 0 0 d 0 0.0
  Discharge 0 1 0 1 d 1 0.5
21 days Cornea Opacity 1 2 2 3 d 4 2.0
  Area 1 4 4 4 d 4 2.8
Iris Value 0 1 0 1 d * 0.4
Conjunctivae Redness 0 0 0 0 d 0 0.0
  Chemosis 0 0 0 0 d 0 0.0
  Discharge 0 0 0 0 d 0 0.0

* Cannot be visualised

d = dead

Table 2 Irritation scores for washed eyes group

      Animal  
Time Effect 7F 8F 9M Mean
24 hours Cornea Opacity 1 2 2 1.7
  Area 4 4 4 4.0
Iris Value 1 1 1 1.0
Conjunctivae Redness 1 1 1 1.0
  Chemosis 2 2 2 2.0
  Discharge 2 2 2 2.0
48 hours Cornea Opacity 3 3 2 2.7
  Area 4 4 4 4.0
Iris Value * * 1 0.3
Conjunctivae Redness 1 1 1 1.0
  Chemosis 3 2 2 2.3
  Discharge 1 2 2 1.7
72 hours Cornea Opacity 3 3 2 2.7
  Area 4 4 4 4.0
Iris Value * * 1 0.3
Conjunctivae Redness 1 1 1 1.0
  Chemosis 2 2 1 1.7
  Discharge 2 2 1 1.7
96 hours Cornea Opacity 3 3 2 2.7
  Area 4 4 4 4.0
Iris Value * * 1 0.3
Conjunctivae Redness 1 1 1 1.0
  Chemosis 2 1 1 1.3
  Discharge 2 1 1 1.3
7 days Cornea Opacity 2 2 2 2.0
  Area 4 4 4 4.0
Iris Value 1 1 1 1.0
Conjunctivae Redness 1 0 0 0.3
  Chemosis 1 0 0 0.3
  Discharge 1 0 1 0.7
10 days Cornea Opacity 2 1 3 2.0
  Area 4 4 3 3.7
Iris Value 1 1 1 1.0
Conjunctivae Redness 1 1 1 1.0
  Chemosis 1 0 0 0.3
  Discharge 1 1 1 1.0
13 days Cornea Opacity 2 1 3 2.0
  Area 4 2 4 3.3
Iris Value 1 0 * 0.3
Conjunctivae Redness 1 0 1 0.7
  Chemosis 1 0 0 0.3
  Discharge 1 1 1 1.0
16 days Cornea Opacity 2 1 3 2.0
  Area 4 2 4 3.3
Iris Value 1 0 * 0.3
Conjunctivae Redness 1 0 0 0.3
  Chemosis 1 0 0 0.3
  Discharge 1 0 0 0.3
19 days Cornea Opacity 2 1 3 2.0
  Area 4 2 4 3.3
Iris Value 1 0 * 0.3
Conjunctivae Redness 1 0 0 0.3
  Chemosis 0 0 0 0.0
  Discharge 1 1 1 1.0
21 days Cornea Opacity 2 1 3 2.0
  Area 4 1 4 3.0
Iris Value 1 0 * 0.3
Conjunctivae Redness 0 0 0 0.0
  Chemosis 0 0 0 0.0
  Discharge 1 0 0 0.3
* Cannot be visualised            

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Remarks:
Migrated information severe eye irritant Criteria used for interpretation of results: EU
Conclusions:
TBHP (aqueous solution as tested) caused severe and irreversible damage to treated eyes in this study. It is a severe eye irritant and it follows that TBHP itself is also a severe eye irritant.
Executive summary:

TBHP (aqueous solution as tested) caused severe and irreversible damage to treated eyes in this study. Based on the available data, TBHP classification as causing serious eye damage (Category 1) is warranted under EC Regulation 1272/2008, CLP.