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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin 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, comparable to current guideline, fully adequate for assessment.
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
skin 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, comparable to current guideline, 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:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
, occlusive testing
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, D-6050 Offenbach/Main, FRG.
- Weight at study initiation: males: 2.99 and 3.47 kg, female: 3.05 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.).
Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites of the same animal
Amount / concentration applied:
0.5 mL of the undiluted test liquid
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
3
Details on study design:
TEST SITE
- Clipping of fur at least 15 hours before the beginning of the study.
- Application area: 2.5 cm x 2.5 cm.
- Application site: Upper third of the region of the back or flank.

REMOVAL OF TEST SUBSTANCE
- Removal of the test substance: At the end of the exposure period with Lutrol and Lutrol/water (1 : 1).

OTHER
- Additional examinations: After sacrifice the animals are examined by gross pathology. If there are clinical signs of necroses, these are confirmed by
gross- pathological examination after incision of the skin. (If there are differences between the clinical and pathological assessments, only the latter is included in the final report.)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 1,2 and 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
- After 72 hours one animal showed scaling in the abdominal and lateral position and dyspnea. This animal was death as a result of dysentery (no substance-related finding) 7 days after the study began.
- The two remaining animals showed scaling at day 8.

Score per animal

Readings

Animal

Erythema

Edema

4 hours

1

1

0

 

2

1

0

 

3

1

0

24 hours

1

1

0

 

2

1

0

 

3

1

0

48 hours

1

0

0

 

2

0

0

 

3

0

0

72 hours

1

0

0

 

2

1

0

 

3

0

0

8 days

1

*

*

 

2

0

0

 

3

0

0

* animal died after 7days

Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not irritant to skin.

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
, occlusive testing
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

Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, D-6050 Offenbach/Main, FRG.
- Weight at study initiation: males: 2.99 and 3.47 kg, female: 3.05 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

Type of coverage:
occlusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin sites of the same animal
Amount / concentration applied:
0.5 mL of the undiluted test liquid
Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
3
Details on study design:
TEST SITE
- Clipping of fur at least 15 hours before the beginning of the study.
- Application area: 2.5 cm x 2.5 cm.
- Application site: Upper third of the region of the back or flank.

REMOVAL OF TEST SUBSTANCE
- Removal of the test substance: At the end of the exposure period with Lutrol and Lutrol/water (1 : 1).

OTHER
- Additional examinations: After sacrifice the animals are examined by gross pathology. If there are clinical signs of necroses, these are confirmed by
gross- pathological examination after incision of the skin. (If there are differences between the clinical and pathological assessments, only the latter is included in the final report.)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 1,2 and 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
- After 72 hours one animal showed scaling in the abdominal and lateral position and dyspnea. This animal was death as a result of dysentery (no substance-related finding) 7 days after the study began.
- The two remaining animals showed scaling at day 8.

Any other information on results incl. tables

Score per animal

Readings

Animal

Erythema

Edema

4 hours

1

1

0

 

2

1

0

 

3

1

0

24 hours

1

1

0

 

2

1

0

 

3

1

0

48 hours

1

0

0

 

2

0

0

 

3

0

0

72 hours

1

0

0

 

2

1

0

 

3

0

0

8 days

1

*

*

 

2

0

0

 

3

0

0

* animal died after 7days

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not irritant to skin.