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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline 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
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
N-butyrylalanine
EC Number:
611-909-2
Cas Number:
59875-04-6
Molecular formula:
C7 H13 N O3
IUPAC Name:
N-butyrylalanine

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: male
- Source: LPT Laboratory of Pharmacology and Toxicology KG, 24601 Löhndorf, Germany
- Age at study initiation: approx. 4.5 months
- Weight at study initiation: 1.9 - 2.5 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 20 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the left eye, which remained untreated, served as control
Amount / concentration applied:
100 mg
Duration of treatment / exposure:
eye was not rinsed after instillation of the test item
Observation period (in vivo):
1, 24, 48 and 72 hours and 4 to 21 days after instillation
Number of animals or in vitro replicates:
3

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1 and #3
Time point:
other: 24, 48, 72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48, 72 h
Score:
>= 3 - <= 4
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritation parameter:
iris score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 18 days
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h
Score:
2
Max. score:
4
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48 h
Score:
1.6
Max. score:
4
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 18 days
Remarks on result:
other: for details see section 'irritant/corrosive reponse data'
Irritant / corrosive response data:
Under the present test conditions a single application of 1 00 mg Butanoylalanin per animal into the conjunctival sac of the right eye of three rabbits caused the following effects:

Corneal opacity
animal no. 1: 1 to 72 hours after instillation (grade 3), 4 to 16 days after Instillation (grade 2) and 17 to 21 days (grade 1);
animal no. 2: 1 and 24 hours after instillation (grade 3), 48 hours to 5 days after instillation (grade 4) and 6 to 21 days (grade 3);
animal no. 3: 1 hour to 5 days after instillation (grade 3), 6 to 14 days after instillation (grade 2) and 15 to 21 days (grade 1 ).
The fluorescein test performed after 24 hours revealed corneal staining in all 3 rabbits (whole surface). The fluorescein test performed after 7 days revealed corneal staining in animal no. 1 (3/4 of the corneal surface) and animal nos. 2 and 3 (whole surface).
The fluorescein tests performed after 14 days revealed corneal staining in animal no. 1 (3/4 of the corneal surface), in animal no. 2 (whole surface) and in animal no. 3 (3/4 of the corneal surface) . The fluorescein tests performed after 21 days revealed corneal staining in animal no. 1 ( 1/2 of the corneal surface), in animal no. 2 (whole surface) and in animal no. 3 (1 /4 of the corneal surface).
An irritation of the iris (grade 2) was observed in all animals 1 hour to 5 days after instillation, in animal no. 1 until 6 days, in animal no. 2 until 21 days after Instillation, (grade 1) in animal no. one 7 to 21 days and in animal no. three 6 to 16 days after Instillation.

Conjunctival redness (grade 1 ) was observed in all three animals 1 hour to 6 days after instillation, in animal no. 2 until 17 days and in animal no. 3 until 14 days after instillation.

Conjunctival chemosis
animal no. 1: 1 hour and 48 hours after instillation (grade 1 ), 24 hours after instillation (grade 2);
animal no. 2: 1 hour and 72 hours to 17 days after instillation (grade 1 ), 24 and 48 hours after instillation (grade. 2);
animal no. 3: 1 hour and 72 hours to 6 days after instillation (grade 1 ), 24 and 48 hours after nstillation (grade 2).
Further observations
Loss of hair at the upper and lower Iids was observed in rabbit no. one 7 to 1 6 days after instillation, in rabbit no. two 7 to 21 days and in rabbit no. three 7 to 11 days after instillation.
Whitish deposits in the conjunctival sac (probably pus) were noted in one rabbit (no. 2) 7 to 9 days after instillation.
Other effects:
No systemic intolerance reactions were observed.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information
Executive summary:

In an eye irritation study according to OECD TG 405 the test substance was instilled into the conjunctival sac of one eye of 3 male rabbits each. Eye irritation was assessed 1, 24, 48 and 72 hours and 4 to 21 days after instillation using the Draize scale. In this study strong irritation was seen as corneal opacity (up to grade 4 of max. 4), effects on iris (up to grade 2 of max. 2), conjunctional redness (up to grade 1 of max. 3) and conjunctional chemosis (up to grade 2 of max. 4). Partly the effects (cornea and iris) appeared to be not reversible within the 21 days observation period. Loss of hair at the upper and lower eye lid and whitish deposits in the conjunctival sac became obvious. No systemic intolerance reactions were observed.

According to classification criteria Butanoylalanin causes serious damage to rabbit's eyes.