Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion: non-GLP, OECD TG 401 (adopted 1981) compliant study, rabbits, 2 -oxoglutaric acid, not classified, effects fully reversible

Eye irritation/corrosion: non-GLP, OECD TG 405 (adopted 1981) compliant study, rabbits, 2 -oxoglutaric acid, severely irritant Cat.1

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984-01-24 to1984-02-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 1981
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: white russian
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4-6 months
- Weight at study initiation: 1.8-2.5 kg
- Housing: singly in stainless steel cages model: Asta
- Diet (e.g. ad libitum): ad libitum, standard chow: ALTROMIN
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 1°C
- Humidity (%): 50-60 %
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded skin
Vehicle:
unchanged (no vehicle)
Controls:
other: left side intact, untreated areas
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg test item moistened with water


Duration of treatment / exposure:
4 hour exposure
Observation period:
up to 14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6.25 cm²/animal
- Type of wrap if used: Areas were covered by linen patches which were fixed with Acylastic, P.Beiersdorf und Co. AG, Hamburg
- Differences to guideline: Abraded and intact skin was treated and observed, but only intact skin was used for evaluation.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing
SCORING SYSTEM:
- Method of calculation: Scoring according to the method of Draize et al., 1944

Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: effects on intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: effects on intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: effects on intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: effects on intact skin
Irritation parameter:
erythema score
Basis:
animal: #2,#3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: effects on intact skin

Table 1: Irritant/corrosive response data for each animal on intact skin at each observation time up to removal of each animal from the test

Score at time point/ Reversibility

Erythema

Edema

 

Max. score: 4

Max. score: 2

24 h

3/0/0

1/0/0

48 h

2/1/1

1/0/0

72 h

1/1/1

0/0/0

Average 24 h, 48 h, 72 h

2/0.67/0.67

0.67/0/0

Reversibility *)

c.

c.

Average time (unit) for reversion

6 days

6 days

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:
GHS criteria not met
Conclusions:
Under the present conditions, occlusive application of the test item for 4 hours to intact and abraded rabbit skin revealed moderate irritating effects (moderate erythrema and slight edema) only in one out of three animals. The other two animals showed no reaction or exhibited a slightly irritating effect, respectively. However, these effects were fully reversible after maximum 6 days. Therefore the test item is not classified according to GHS citeria.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 1981
GLP compliance:
not specified
Species:
rabbit
Strain:
other: white russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6 month
- Weight at study initiation: 2.1-2.2 kg
- Housing: singly in stainless steel cages model: ASTA
- Diet (e.g. ad libitum): sniff (K) Alleindiät für Kaninchen, ad libitum
- Water (e.g. ad libitum): Trinkwasserqualität der Stadtwerke Bielefeld, ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of the test substance was instilled in the conjunctival sac of the right eye.
Duration of treatment / exposure:
100 mg of the test article (undiluted) was placed in the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article. The eyes were not rinsed.
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3 female rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): There was no washing of the eyes.
- Scoring system: OECD TG 405 / Draize scale
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: observed petechiae
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Max. score:
2
Remarks on result:
other: could not be evaluated due to corneal opacity
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Max. score:
2
Remarks on result:
other: could not be evaluated due to corneal opacity
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: ulcerous and necrotic areas
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: ulcerous and necrotic areas
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: completely closed eyes
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: completely closed eyes
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Other effects:
- Other observations: Severe reactions after instillation of the substance, adverse effects on the iris could not be detected due to the non-reversible, strong opacity of the cornea.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time

point /

Reversibility

Cornea

Iris

Conjuctivae

Chemosis

 

Max. score: 4

Max. score: 3

Max. score: 3

Max. score: 4

60 min

4/3/3

1/1/1

0/0/0

2/2/2

24 h

3/3/3

**) n.d./n.d./1

3/3/2

3/3/3

48 h

4/4/3

n.d./n.d./1

3/3/2

4/4/3

72 h

4/4/3

n.d./n.d./1

3/3/2

4/4/3

Average 24 h, 48 h, 72 h

3.67/3.67/3

n.d./n.d./1

3/3/2

3.67/3.67/3

Reversibility

n.

n.

n.

n.

Average time (unit) for reversion

n.

n.

n.

n.

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**) n.d. = not detectable

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test substance was tested for eye irritation in a study according to OECD guideline 405 (Acute Eye Irritation / Corrosion). The substance was instilled into the conjunctival sac of three white russian rabbits. The opacity of the cornea was severe among the animals and the effect was not reversible within 21 days in two of the rabbits. Chemosis and conjunctival effects were also severe and not reversible within 21 days. In this study the test item has irreversible severe effects on the eye and is therefore classified in Category 1.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the available data 2 -oxoglutaric acid is classified as non-irritating to the skin but is categorized to cause serious damage to the eyes (Category 1) and labelled with H318 (Causes serious eye damage) according to Regulation (EC) 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labeling of Chemicals (GHS).