(-)-3,7-dimethyloct-6-en-1-ol

Endpoint summary

Description of key information

These endpoints were fulfilled using read across from Citronellol (3,7-dimethyl-6-Octen-1-ol, CAS 106 -22 -9).

Acute oral toxicity

The acute oral toxicity of the substance was assessed in rats at doses 2025 – 5000 mg/kg bw. The LD 50 was 3450 mg/kg bw.

Acute dermal toxicity

The acute dermal toxicity was assessed in rabbits according toe the standard acute method. Doses of 1250, 2500 and 5000 mg.kg bw were tested. The LD 50 value was 2650 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1973

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study conducted in 1973.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

2025, 2560, 3200, 4000, 5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 450 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 210 - <= 3 690

Mortality:

5000 mg/kg bw: 8/10
4000 mg/kg bw: 6/10
3200 mg/kg bw: 7/10
2560 mg/kg bw: 0/10
2050 mg/kg bw: 1/10

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 is >2000 mg/kg bw, the substance cannot be classified according to the CLP criterias.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1973

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source substances and target substance have similar physical-chemical properties and (eco)toxicological properties because they are either stereoisomers of the target substance, are hydrolysed to the same substance or their chemical structure differs only by an additional double bond. This prediction is supported by data on the substances themselves.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance, L-Citronellol, is a mono-constituent substance (EC No. 231-415-7, CAS no. 7540-51-4 consisting of a C8 carbon backbone, methyl substituents at C3 and C7, one double bond and a hydroxyl group. The substance is optically active, comprising a single, pure enantiomeric laevo form.

The source substance, DL-Citronellol, is a mono-constituent substance (EC No. 203-375-0, CAS no. 106-22-9, consisting of a C8 carbon backbone, methyl substituents at C3 and C7, one double bond and a hydroxyl group. The substance is an equimolar mixture of two optical isomers (enantiomers).

The source substance, citronellyl acetate, is a mono-constituent substance (EC No. 205-775-0, CAS no. 150-84-5) consisting of a C8 carbon backbone, methyl substituents at C3 and C7, one double bond and an acetate group.

The source substance, geraniol and it’s isomer, consist of a C8 carbon backbone, methyl substituents at C3 and C7, two double bonds and a hydroxyl group. The only difference between the isomers is the position of the first double bond.

The source substance, geraniol and nerol, is a multi-constituent substance of E/Z isomers (EC No. 906-125-5). The constituents consist of a C8 carbon backbone, methyl substituents at C3 and C7, two double bonds and a hydroxyl group.

The source substance, geraniol, is a mono-constituent substance (EC No. 203-377-1, CAS no. 106-24-1), consisting of a C8 carbon backbone, methyl substituents at C3 and C7, two double bonds and a hydroxyl group. Geraniol is a pure form of the E-isomer.

The source substance, nerol, is a mono-constituent substance (EC No. 203-378-7, CAS no. 106-25-2), consisting of a C8 carbon backbone, methyl substituents at C3 and C7, two double bonds and a hydroxyl group. Nerol is a pure form of the Z-isomer.
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 source substances only differ in the enantiomeric ratio or an additional double bond. Another source substance is expected to be hydrolysed to the same structure as the target substance.
In a non-chiral environment the target and source chemical DL-Citronellol 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). All endpoints read-across from DL-Citronellol are considered to be acceptable for this substance assuming that 50% of the target compound is available in the test material.
The source substance citronellyl acetate is read-across from as part of a weight of evidence approach in the repeated dose toxicity endpoint. As this substance is hydrolysed to Citronellol within 2 hours, this read-across endpoint is acceptable in the weight of evidence approach used.
The source substances geraniol, nerol and the reaction mass of geraniol/nerol differ from the target substance only by an additional double bond at C2. These structures are considered to represent a worst case scenario due to the additional potential reactive feature of the second double bond. The genotoxicity, repeated dose and reproductive toxicity endpoints read-across from these substances are therefore acceptable as a worst case assumption.

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 followed

Principles of method if other than guideline:

Study conducted in 1973.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

2025, 2560, 3200, 4000, 5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

3 450 mg/kg bw

Based on:

test mat.

95% CL:

>= 3 210 - <= 3 690

Mortality:

5000 mg/kg bw: 8/10
4000 mg/kg bw: 6/10
3200 mg/kg bw: 7/10
2560 mg/kg bw: 0/10
2050 mg/kg bw: 1/10

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 is >2000 mg/kg bw, the substance cannot be classified according to the CLP criterias.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 450 mg/kg bw

Quality of whole database:

Read across from Citronellol (3,7-dimethyl-6-Octen-1-ol, CAS 106 -22 -9).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

acute dermal toxicity study carried out in 1973.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Duration of exposure:

no data

Doses:

1250, 2500, 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 650 mg/kg bw

95% CL:

>= 1 780 - <= 3 520

Mortality:

5000 mg/kg bw: 5/5
2500 mg/kg bw: 2/5
1250 mg/kg bw: 0/5

Clinical signs:

other: 5000 mg/kg bw: ataxia and pupillary dilation 2500 mg/kg bw: ataxia in 4 animals 1250 mg/kg bw: 2 animals were weak and unable to stand

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

According to this study, the substance cannot be classified by the CLP classification.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source substances and target substance have similar physical-chemical properties and (eco)toxicological properties because they are either stereoisomers of the target substance, are hydrolysed to the same substance or their chemical structure differs only by an additional double bond. This prediction is supported by data on the substances themselves.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance, L-Citronellol, is a mono-constituent substance (EC No. 231-415-7, CAS no. 7540-51-4 consisting of a C8 carbon backbone, methyl substituents at C3 and C7, one double bond and a hydroxyl group. The substance is optically active, comprising a single, pure enantiomeric laevo form.

The source substance, DL-Citronellol, is a mono-constituent substance (EC No. 203-375-0, CAS no. 106-22-9, consisting of a C8 carbon backbone, methyl substituents at C3 and C7, one double bond and a hydroxyl group. The substance is an equimolar mixture of two optical isomers (enantiomers).

The source substance, citronellyl acetate, is a mono-constituent substance (EC No. 205-775-0, CAS no. 150-84-5) consisting of a C8 carbon backbone, methyl substituents at C3 and C7, one double bond and an acetate group.

The source substance, geraniol and it’s isomer, consist of a C8 carbon backbone, methyl substituents at C3 and C7, two double bonds and a hydroxyl group. The only difference between the isomers is the position of the first double bond.

The source substance, geraniol and nerol, is a multi-constituent substance of E/Z isomers (EC No. 906-125-5). The constituents consist of a C8 carbon backbone, methyl substituents at C3 and C7, two double bonds and a hydroxyl group.

The source substance, geraniol, is a mono-constituent substance (EC No. 203-377-1, CAS no. 106-24-1), consisting of a C8 carbon backbone, methyl substituents at C3 and C7, two double bonds and a hydroxyl group. Geraniol is a pure form of the E-isomer.

The source substance, nerol, is a mono-constituent substance (EC No. 203-378-7, CAS no. 106-25-2), consisting of a C8 carbon backbone, methyl substituents at C3 and C7, two double bonds and a hydroxyl group. Nerol is a pure form of the Z-isomer.
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 source substances only differ in the enantiomeric ratio or an additional double bond. Another source substance is expected to be hydrolysed to the same structure as the target substance.
In a non-chiral environment the target and source chemical DL-Citronellol 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). All endpoints read-across from DL-Citronellol are considered to be acceptable for this substance assuming that 50% of the target compound is available in the test material.
The source substance citronellyl acetate is read-across from as part of a weight of evidence approach in the repeated dose toxicity endpoint. As this substance is hydrolysed to Citronellol within 2 hours, this read-across endpoint is acceptable in the weight of evidence approach used.
The source substances geraniol, nerol and the reaction mass of geraniol/nerol differ from the target substance only by an additional double bond at C2. These structures are considered to represent a worst case scenario due to the additional potential reactive feature of the second double bond. The genotoxicity, repeated dose and reproductive toxicity endpoints read-across from these substances are therefore acceptable as a worst case assumption.

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 followed

Principles of method if other than guideline:

acute dermal toxicity study carried out in 1973.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Duration of exposure:

no data

Doses:

1250, 2500, 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 650 mg/kg bw

95% CL:

>= 1 780 - <= 3 520

Mortality:

5000 mg/kg bw: 5/5
2500 mg/kg bw: 2/5
1250 mg/kg bw: 0/5

Clinical signs:

other: 5000 mg/kg bw: ataxia and pupillary dilation 2500 mg/kg bw: ataxia in 4 animals 1250 mg/kg bw: 2 animals were weak and unable to stand

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

According to this study, the substance cannot be classified by the CLP classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 650 mg/kg bw

Quality of whole database:

Read across from Citronellol (3,7-dimethyl-6-Octen-1-ol, CAS 106 -22 -9).

Justification for classification or non-classification

In the CLP regulation acute toxicity means those adverse effects occurring following oral or dermal administration of a single dose of a substance or a mixture, or multiple doses given within 24 hours, or an inhalation exposure of 4 hours.

The substance does not meet the criteria for classification under the CLP regulations for acute toxicity via the oral route based on the result of an acute oral toxicity study, which gave a LD50 of 3450 mg/kg bodyweight, which is above the classification cut-off value ( ≤ 2000 mg/kg bodyweight) for acute oral toxicity.

The substance does not meet the criteria for classification under the CLP regulations for acute toxicity via the dermal route based on the result of a dermal toxicity study, which gave a LD50 of 2650 mg/kg bodyweight, which is above the classification cut-off value ( ≤ 2000 mg/kg bodyweight) for acute dermal toxicity.