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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:
From 31 Jan, 1994 to 14 Feb, 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Three healthy adult rabbits of the New Zealand White strain were obtained from Froxfield (U .K.) Ltd., Petersfield, Hampshire, England.
- Age at study initiation: 12 to 15 weeks
- Weight at study initiation: 2.8 to 3.4 kg
- Housing: Housed individually in plasticcages with perforated floors in buliding R 14 room 1
- Diet: Ad libitum, satndard laboratory diet SDS stanrab (P) rabbit diet (diet was not analysed for nutrients, contaminants or micro-organisms)
- Water: Ad libitum, routine chemical examination of drinking water at source was conducted usually weekly by the supplier
- Acclimation period: Yes

ENVIRONMENTAL CONDITIONS
- Temperature: 19°C
- Humidity: 30 to 70%
- Air changes (per hr): 19 changes/h
- Photoperiod (hrs dark / hrs light): 12 h of artificial light (0700 - 1900 h) in each 24 h period.

Each animal was identified by a numbered aluminium tag placed through the edge of one ear.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL undiluted
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
Observations were made 1, 24, 48 and 72 h after exposure.
Number of animals or in vitro replicates:
3
Details on study design:
-Treatment: The eyes of each animal was examined prior to instillation of the test substance to ensure that there is no pre-existing corneal damage, iridial or conjunctival inflammation.
- One animal was tested in advance to ensure that if a severe response was produced no further animals would be exposed.

- Single instillation of 0.1 mL undiluted test substance was made in the lower everted lid of one eye of each animal. The lids were then gently held together for about 1 sec to prevent loss of the test substance. The contralateral eye remained untreated.

-Observation:
Clinical signs: Once daily.
Ocular responses: The eyes of each animal were examined approx 1, 24, 48 and 72 h and after 4 and 7 d after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded. Observations of the eyes was aided by the use of a handheld light.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.66
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.66
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 2.33
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1.63
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritant / corrosive response data:
Irritation: Instillation of approx 0.1 mL undiluted test substance into one eye of each of three rabbits resulted in corneal opacities, transient iridial inflammation, a diffuse crimson or beefy red coloration of the conjunctivae accompanied by swelling with partial eversion of the eyelids or with the eyelids closed. The eyes became normal 7 d after instillation.
Other effects:
No signs of toxicity or ill health were observed in any rabbit during the observation period.

Any other information on results incl. tables

Results:

Rabbit number

Region of eye

1 h

24 h

48 h

72 h

4 d

7 d

27 (male)

Cornea

dulling

1

1

1

1

0

Iris

0

1

0

0

0

0

Conjunctivae (redness)

2

3

2

1

1

0

Conjunctivae (chemosis)

2

3

2

1

0

0

81 (female)

Cornea

0

1

1

1

1

0

Iris

0

1

1

0

0

0

Conjunctivae (redness)

2

2

3

2

2

0

Conjunctivae (chemosis)

2

2

2

1

1

0

82 (female)

Cornea

0

0

1

1

1

0

Iris

0

0

0

1

0

0

Conjunctivae (redness)

2

2

2

2

2

0

Conjunctivae (chemosis)

2

1

1

1

1

0

Applicant's summary and conclusion

Interpretation of results:
other: Category 2 (irritating to eyes) based on CLP criteria
Conclusions:
Under the test conditions, undiluted di-TMPTTA was found to be irritating to the eye of rabbit under CLP (EC 1272/2008) but not under EC (67/548/EEC) criteria.
Executive summary:

A study was performed to assess the eye irritation potential of di-TMPTTA in New Zealand White rabbits according to OECD Guideline 405 and EU Method B.5, in compliance with GLP. 0.1 mL undiluted test substance was placed in the lower everted lid of one eye of each of three animals. The lids were then gently held together for about 1 s to prevent loss of the test substance. The contralateral eye remained untreated and served as a negative control. Instillation resulted in corneal opacities, transient iridial inflammation, and diffuse crimson or beefy red coloration of the conjunctivae accompanied by swelling with partial eversion of the eyelids or with the eyelids closed. The eyes returned to normal 7 d after instillation. Given a conjunctival redness score ≥ 2 but ≤ 2.5 in 2 out of 3 animals, calculated as the mean score following grading at 24, 48 and 72 h and reversible within 21 days, the test substance was considered to be irritating to the eyes of rabbits under CLP (EC 1272/2008) but not under EC (67/548/EEC) criteria (Parcell 1994).