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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:
1999-09-20 to 1999-12-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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 (incl. QA statement)

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:
succinic acid
Constituent 4
Reference substance name:
Bernsteinsaure kristallin
IUPAC Name:
Bernsteinsaure kristallin
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 (%): no details
- 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):
within 24 hours before instillation and 1, 24, 48 and 72 hours after instillation. Additional examinations were performed 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 (see Table 1 in section Any other information on materials and methods incl. tables)

TOOL USED TO ASSESS SCORE: otoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
reactions persisted to termination on day 21
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
other: Extensive corneal opacity persisted to termination on day 21 precluding assessment or ophthalmological examination of the iris.
Remarks on result:
not determinable
Remarks:
It was not possible to provide a score for iridial change recorded due to extensive corneal opacity to termination on day 21 precluding assessment or ophthalmological examination of the iris. A maximum score of 2 was assumed.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
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:
24/48/72 h
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:
As severe eye lesions were observed, only one rabbit was treated with the test substance. 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
Conclusions:
In an acute eye irritation/corrosion study, instillation of succinic acid to one rabbit eye resulted in severe and persistent irritant reactions that require classification of the test material as Cat. 1 (serious damage to eyes) according to CLP criteria as set out in Regulation 1272/2008.
Executive summary:

In a primary eye irritation/corrosion study performed according to OECD TG 405, 100 mg of succinic acid (purity: min. 99.5%) was instilled into the conjunctival sac of the right eye of one female New Zealand White rabbit for 24 hours. After the instillation of the test substance, the conjunctival sacs of both eyes were rinsed with warm tap water to remove residual test substance. Anmals were then observed for 21 days. Irritation was scored by the method of Draize.

Severe and irreversible corneal alterations were observed until day 21. The iris was not discernible because of severe corneal opacity. Pronounced conjunctival redness was observed which gradually decreased in severity but did not fully resolve. Severe conjunctival swelling was noted which was reversible until day 15. In addition, a dermal swelling dorsal of the test eye was noted.

In this study, succinic acid caused severe damage to the eye, based on irreversible ocular lesions that failed to fully resolve within 21 days after instillation.

Based on these results, classification of succinic anhydride as Cat. 1 (serious damage to eyes) is warranted according to CLP criteria as set out in Regulation 1272/2008.