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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:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP compliant guideline study, fully adequate for assessment.
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP compliant guideline study, fully adequate for assessment.
Justification for type of information:
ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The structures of the target and source substances are identical and differ only with respect to the ratio of enantiomers where the target substance is a single pure L-isomer and the source substance is an equimolar mixture of L and D isomers.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance, L-Citronellyl nitrile, is a mono-constituent substance (EC No. 695-909-8, CAS no. 35931-93-2).
The source substance, DL-Citronellyl nitrile, is a mono-constituent substance (EC No. 257-288-8, CAS no. 51566-62-2).
The source and target substances are both of high purity with a low concentration of impurities.

3. ANALOGUE APPROACH JUSTIFICATION
The read across hypothesis is based on structural similarity where the only difference between target and source molecules is the enantiomeric ratio. In a non-chiral environment the target and source chemicals will have identical properties but in the chiral environment of living organisms the enantiomers may possess different carcinogenicity and teratogenicity (in a chiral environment, stereoisomers might experience selective absorption, protein binding, transport, enzyme interactions and metabolism, receptor interactions, and DNA binding). Therefore, as a precaution for the developmental toxicity endpoint it is suggested that the NOAEL 250 mg/kg bw/day for L-Citronellyl nitrile is used instead of 500 mg/kg bw/day, as it is not known which form is more potent in vivo. All other endpoints are considered to be acceptable for this substance assuming that 50% of the target compound is available in the test material.

4. DATA MATRIX
Please refer to the data matrix included in the read-across justification document attached in Section 13.2.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
, limited observation time
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler, D-6050 Offenbach/Main, FRG.
- Weight at study initiation: males: 2.85 and 2.98 kg, female: 3.27 kg.
- Housing: Individually in stainless steel cages with wire mesh walk floor (floor area: 40 cm x 51 cm). No bedding in the cages; sawdust in the waste trays.
- Diet: Ovator Solikanin 4 mm; Muskator-Werke, D-4000 Düsseldorf 1, FRG (about 130 g per animal daily).
- Water: About 250 mL tap water per animal daily.
- Acclimation period: About 8 days before the beginning of the study in the skin laboratory; same housing conditions as during the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24.
- Humidity (%): 30 - 70.
- Photoperiod (hrs dark / hrs light): 12 h/12 h (6.00a.m. - 18.00p.m./18 p.m. - 8a.m.).
Vehicle:
unchanged (no vehicle)
Controls:
other: Negative control: Untreated eye.
Amount / concentration applied:
Undiluted
Amount applied: 0.1 mL
Duration of treatment / exposure:
8 days
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3
Details on study design:
Application site: Conjunctival sac of the right eyelid.
No wash out of substance.
Irritation parameter:
cornea opacity score
Basis:
animal: 1-3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal: 1-3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal: 1-3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable

Individual eye irritation scores:

Readings

Animal

Cornea

Iris

Conjunctiva

 

 

Opacity

Area

 

Redness

Swelling

Discharge

1 hours

1

0

0

0

3

1

2

 

2

0

0

0

3

1

2

 

3

0

0

0

3

1

2

24 hours

1

0

0

0

1

0

0

 

2

0

0

0

1

0

0

 

3

0

0

0

1

0

0

48 hours

1

0

0

0

1

0

0

 

2

0

0

0

1

0

0

 

3

0

0

0

1

0

0

72 hours

1

0

0

0

1

0

0

 

2

0

0

0

1

0

0

 

3

0

0

0

1

0

0

8 days

1

0

0

0

1

0

0

 

2

0

0

0

1

0

0

 

3

0

0

0

1

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not classified for eye irritation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
, limited observation time
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Citronellylnitril
- Test substance No.: 82/88
- Stable until: March 1984

Test animals / tissue source

Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler, D-6050 Offenbach/Main, FRG.
- Weight at study initiation: males: 2.85 and 2.98 kg, female: 3.27 kg.
- Housing: Individually in stainless steel cages with wire mesh walk floor (floor area: 40 cm x 51 cm). No bedding in the cages; sawdust in the waste trays.
- Diet: Ovator Solikanin 4 mm; Muskator-Werke, D-4000 Düsseldorf 1, FRG (about 130 g per animal daily).
- Water: About 250 mL tap water per animal daily.
- Acclimation period: About 8 days before the beginning of the study in the skin laboratory; same housing conditions as during the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24.
- Humidity (%): 30 - 70.
- Photoperiod (hrs dark / hrs light): 12 h/12 h (6.00a.m. - 18.00p.m./18 p.m. - 8a.m.).

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Negative control: Untreated eye.
Amount / concentration applied:
Undiluted
Amount applied: 0.1 mL
Duration of treatment / exposure:
8 days
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3
Details on study design:
Application site: Conjunctival sac of the right eyelid.
No wash out of substance.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 1-3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal: 1-3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal: 1-3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable

Any other information on results incl. tables

Individual eye irritation scores:

Readings

Animal

Cornea

Iris

Conjunctiva

 

 

Opacity

Area

 

Redness

Swelling

Discharge

1 hours

1

0

0

0

3

1

2

 

2

0

0

0

3

1

2

 

3

0

0

0

3

1

2

24 hours

1

0

0

0

1

0

0

 

2

0

0

0

1

0

0

 

3

0

0

0

1

0

0

48 hours

1

0

0

0

1

0

0

 

2

0

0

0

1

0

0

 

3

0

0

0

1

0

0

72 hours

1

0

0

0

1

0

0

 

2

0

0

0

1

0

0

 

3

0

0

0

1

0

0

8 days

1

0

0

0

1

0

0

 

2

0

0

0

1

0

0

 

3

0

0

0

1

0

0

Applicant's summary and conclusion