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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 30, 1979 - January 4, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According to study described in Materials and methods
Cross-reference
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
November 30, 1979 - January 4, 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: According to study described in Materials and methods
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:
no guideline available
Principles of method if other than guideline:
Twelve Hartley guinea pigs, male, 294-470 grams, acclimated for 7 days, each received a series of 10 intradermal injections of the test article, in 0.1% suspension in physiological saline, over a 3 week period. Two weeks after the last injection, a challenge injection was made. Obeservations of the diameter and height (in millimiters) and color (erythema) of any reaction at the injection site were recorded 24 hours after each treatment.
GLP compliance:
yes
Type of study:
Draize test
Justification for non-LLNA method:
Study carried out in 1980.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 4 to 6 weeks of age
- Weight at study initiation: 294 - 470 grams
- Housing: galvanized or stainless steel cages
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: 7 days
- Indication of any skin lesions: checked upon receipt and prior to test initiation
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1%
Day(s)/duration:
3 weeks
Adequacy of induction:
not specified
No.:
#1
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.05 mL
Day(s)/duration:
1
Adequacy of challenge:
not specified
No. of animals per dose:
10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 3 weeks
- Test groups: 12 animals
- Control group: none
- Site: mid-dorsal area of the trunk, 3 or 4 centimeters square
- Duration: 3 weeks.
- Concentrations: 0.1%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 hours
- Test groups: 10 animals
- Control group: none
- Concentrations: 0.05 mL
- Evaluation: 24 hours
Challenge controls:
none
Positive control substance(s):
no
Positive control results:
Not applicable
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
12
Clinical observations:
Animal #1 - #12: No gross changes observed.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Group:
negative control
Remarks on result:
other: not applicable
Key result
Reading:
1st reading
Group:
positive control
Remarks on result:
other: not applicable

See attachment for result tables.

Interpretation of results:
GHS criteria not met
Conclusions:
The readings at the challenge were not higher than the average readings for the 10 induction injection, the test article was not considered a sensitizer in guinea pigs.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report date:
1980

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Twelve Hartley guinea pigs, male, 294-470 grams, acclimated for 7 days, each received a series of 10 intradermal injections of the test article, in 0.1% suspension in physiological saline, over a 3 week period. Two weeks after the last injection, a challenge injection was made. Obeservations of the diameter and height (in millimiters) and color (erythema) of any reaction at the injection site were recorded 24 hours after each treatment.
GLP compliance:
yes
Type of study:
Draize test
Justification for non-LLNA method:
Study carried out in 1980.

Test material

Constituent 1
Chemical structure
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: Citronellal Nitril

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 4 to 6 weeks of age
- Weight at study initiation: 294 - 470 grams
- Housing: galvanized or stainless steel cages
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: 7 days
- Indication of any skin lesions: checked upon receipt and prior to test initiation

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1%
Day(s)/duration:
3 weeks
Adequacy of induction:
not specified
Challenge
No.:
#1
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.05 mL
Day(s)/duration:
1
Adequacy of challenge:
not specified
No. of animals per dose:
10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 3 weeks
- Test groups: 12 animals
- Control group: none
- Site: mid-dorsal area of the trunk, 3 or 4 centimeters square
- Duration: 3 weeks.
- Concentrations: 0.1%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 hours
- Test groups: 10 animals
- Control group: none
- Concentrations: 0.05 mL
- Evaluation: 24 hours
Challenge controls:
none
Positive control substance(s):
no

Results and discussion

Positive control results:
Not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
12
Clinical observations:
Animal #1 - #12: No gross changes observed.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Group:
negative control
Remarks on result:
other: not applicable
Key result
Reading:
1st reading
Group:
positive control
Remarks on result:
other: not applicable

Any other information on results incl. tables

See attachment for result tables.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The readings at the challenge were not higher than the average readings for the 10 induction injection, the test article was not considered a sensitizer in guinea pigs.

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