Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 July - 1 December 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study according to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Bernsteinsaure = Succinic acid
IUPAC Name:
Bernsteinsaure = Succinic acid
Constituent 2
Reference substance name:
1,4-butane-di-carbonic-acid
IUPAC Name:
1,4-butane-di-carbonic-acid
Constituent 3
Chemical structure
Reference substance name:
Succinic acid
EC Number:
203-740-4
EC Name:
Succinic acid
Cas Number:
110-15-6
Molecular formula:
C4H6O4
IUPAC Name:
butanedioic acid
Details on test material:
- Name of test material (as cited in study report): Bernsteinsaure = succinic acid

- Physical state: white crystalline powder
- Analytical purity: 99.5%
- Impurities (identity and concentrations): water

- Purity test date: no details
- Lot/batch No.: SLMB 112
- Expiration date of the lot/batch: December 1999

- Stability under test conditions: stable for duration of study
- Storage condition of test material: in refrigerator in dark
- Other: Density at 20°C = 1.56 g/cm3. pH 2.7 (1% w/v dispersion in water)

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga
- Age at study initiation: Not stated
- Weight at study initiation: 2.9 kg
- Housing:Individual metal wire caging
- Diet (e.g. ad libitum): Altromin 2023 ad libitum
- Water (e.g. ad libitum): tap water via automatic watering system - ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean 20°C
- Humidity (%): Mean 63 %
- Air changes (per hr): 12/h
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 20 September 1999 To: 12 October 1999

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL (equivalent to a weight of 100 mg)
Duration of treatment / exposure:
Eye held closed to prevent immediate ejection of dose. Treated eye was rinsed with water 24 hours after instillation to remove any residual material.
Observation period (in vivo):
1, 24, 48 and 72 hours after instillation and then 6, 8, 10, 13, 15 and 21 days after dosing
Number of animals or in vitro replicates:
One female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated eye rinsed 24 hours after instillation

SCORING SYSTEM: Standard modified Draize ocular assessment scale

TOOL USED TO ASSESS SCORE: otoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24-72 h and day 21
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
reactions persisted to termination on day 21
Remarks on result:
other: reactions persisted to termination on day 21
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
2
Max. score:
2
Reversibility:
other: corneal reactions persisted to termination on day 21, it is assumed that iridial reactions would also persist
Remarks on result:
other: It was not possible to provide a score for iridial change recorded due to extensive corneal opacity precluding assessment or ophthalmological examination of the iris, it is assumed that a maximum score of 2 would have been assigned.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24-72 h and to day 21
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
other: Although reactions showed some amelioration over the three week observation period, some conjunctivitis remained at termination
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24-72 h and up to day 21
Score:
3.7
Max. score:
4
Reversibility:
fully reversible within: 15 days
Remarks on result:
other: marked chemosis persisted to 72 h after instillation but reactions lessened over the first week and the conjunctival swelling had overtly resolved by day 15
Irritant / corrosive response data:
Only one rabbit was treated. Corneal opacification affected the entire corneal surface from Day 1 to Day 21 with no resolution or improvement. The severity of the corneal obfuscation precluded any assessment of iris response or iridial changes. Conjunctival reactions include a diffuse beefy red discoloration that persisted for 6 days and gradually reduced in severity but did not fully resolve before termination on day 21. The degree of conjunctival swelling, initially severe, improved slowly and had resolved fully by day 15
Other effects:
At 48 and 72 hours the region located dorsally to the treated eye was also swollen

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Instillation of succinic acid to one rabbit eye resulted in severe and persistent irritant reaction. According to these results and to the Directive 93/21/EEC, the test substance poses a "risk of serious damage to eyes".
Executive summary:

In a single rabbit eye irritation test, conducted in accordance with OECD and EU test guidelines, persistent reactions were observed that failed to fully resolve within 21 days of instillation.

According to these results and to the Directive 93/21/EEC, the test substance poses a "risk of serious damage to eyes".