(3R)-3,7-dimethyloct-6-enenitrile

Skin irritation / corrosion

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 for cross-reference:

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 for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

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 or test system 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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

, occlusive testing

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,7-dimethyloct-6-enenitrile

EC Number:

257-288-8

EC Name:

3,7-dimethyloct-6-enenitrile

Cas Number:

51566-62-2

Molecular formula:

C10H17N

IUPAC Name:

3,7-dimethyloct-6-enenitrile

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 or test system 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

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 4

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.