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

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Scientifically acceptable publication, however only a summary is available in english.

Reason / purpose for cross-reference:

reference to same study

Principles of method if other than guideline:

Acute toxicity to fish

GLP compliance:

not specified

Analytical monitoring:

not specified

Test organisms (species):

Cyprinus auratus

Test type:

static

Water media type:

freshwater

Test temperature:

20 °C

Duration:

1 h

Dose descriptor:

other: TT

Effect conc.:

8.6 mg/L

Reference 2

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedures in compliance with German national standards, however no chemical analysis of the test substance in the test medium was carried out. Non-GLP study.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: German standard DIN 38 412, part L15.

GLP compliance:

no

Analytical monitoring:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: The test solution was prepared by adding the test item to the test media without any pre-treatment. Subsequently the fish were placed into the test aquaria.

Test organisms (species):

Leuciscus idus

Details on test organisms:

TEST ORGANISM
- Common name: Golden orfe
- Source: Fish farm Paul Eggers, 2354 Hohenwestedt, Germany
- Length at study initiation (length definition, mean, range and SD): 6.7 cm (range 6.0 - 7.2 cm)
- Weight at study initiation (mean and range, SD): 2.8 g (range 2.0 - 3.6 g)
- Method of breeding: oil-free aerated and charcoal filtered tap water, flow-through system Water temperature: 19 - 21 °C Duration of housing: about 3 months Mortality during the last 2 weeks of housing: 0.08 %; Medical treatment: Twice with 0.05 mg/l malachite green chloride, once with 10 mg/l tetracycline hydrochloride
Corpulence factor of the test fish batch: 0.9
- Feeding during test: 1 day before and during exposure.

ACCLIMATION
- Acclimation period: 3 days
- Type and amount of food: Growing feed F/B 50, ad libitum.
- Health during acclimation (any mortality observed): no mortality observed

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Hardness:

2.5 mmol/l

Test temperature:

20 - 21 °C

pH:

7.3 - 7.7

Dissolved oxygen:

7.8 - 8.6 mg/l

Nominal and measured concentrations:

Nominal test concentrations (mg/l):
4.64, 10, 21.5, 46.4, 100, control

Details on test conditions:

TEST SYSTEM
- Test vessel: glass aquaria (30 x 22 x 24 cm)
- Fill volume: 10 l
- Aeration: Continuous aeration with oil-free air
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1
- Biomass loading rate: 2.8 g fish/l test water


TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: reconstituted freshwater according to DIN 38412, Part II, 1982; prepared from fully demineralised tap water (conductivity: max 10 micro MHO) by adding: 294.0 mg/l CaCl2 * 2 H2O 123.3 mg/l MgSO4 + 7 H2O 63.0 mg/l NaHCO3 5.5 mg/l KCl
- Ca/mg ratio: 4 : 1


OTHER TEST CONDITIONS
- Photoperiod: 16 : 8 hours day-night regime


EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Mortality and symptoms of intoxication after 1, 4, 24, 48, 72 and 96 hours

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

4.6 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC0

Effect conc.:

10 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

14.66 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

21.5 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Results with reference substance (positive control):

48 h-LC50 of the positive control chloroacetamide: about 32 mg/l (corresponds to normal sensitivity).

Reported statistics and error estimates:

The LC50 value was calculated as the geometrical mean of LC0 (10 mg/l) and LC100 (21.5 mg7l) nominal values.

Sublethal observations / clinical signs:

During the 96 h exposure to citronellol, mortalities were as follows:

Nominal test / Cumulative mortality (%) after x hours
concentration / 1 / 4 / 24 / 48 / 72 / 96 /
(mg/l)
Control / 0 / 0 / 0 / 0 / 0 / 0 /
4.64 / 0 / 0 / 0 / 0 / 0 / 0 /
10.0 / 0 / 0 / 0 / 0 / 0 / 0 /
21.5 / 100 / 100 / 100 / 100 / 100 / 100 /
46.4 / 100 / 100 / 100 / 100 / 100 / 100 /
100.0 / 100 / 100 / 100 / 100 / 100 / 100 /

Symptoms of intoxication:

Nominal test / Symptoms of intoxication after x hours
concentration / 1 / 4 / 24 / 48 / 72 / 96 /
(mg/l)
Control / - / - / - / - / - / - /
4.64 / - / - / - / - / - / - /
10.0 / A / A / A / - / - / - /
21.5 / + / + / + / + / + / + /
46.4 / + / + / + / + / + / + /
100.0 / + / + / + / + / + / + /

Definitions of Symptoms:
-: No symptoms
A: Apathy
+: All fish dead

Chemical Analysis
No analytical dose-verification of the test item was carried out. Therefore all biological results refer to nominal test concentrations of Citronellol.

Reference 3

Endpoint:

short-term toxicity to fish

Type of information:

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

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Scientifically acceptable publication, however only a summary is available in english.

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

Principles of method if other than guideline:

Acute toxicity to fish

GLP compliance:

not specified

Analytical monitoring:

not specified

Test organisms (species):

Cyprinus auratus

Test type:

static

Water media type:

freshwater

Test temperature:

20 °C

Duration:

1 h

Dose descriptor:

other: TT

Effect conc.:

8.6 mg/L

Reference 4

Endpoint:

short-term toxicity to fish

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedures in compliance with German national standards, however no chemical analysis of the test substance in the test medium was carried out. Non-GLP study.

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:

according to guideline

Guideline:

other: German standard DIN 38 412, part L15.

GLP compliance:

no

Analytical monitoring:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: The test solution was prepared by adding the test item to the test media without any pre-treatment. Subsequently the fish were placed into the test aquaria.

Test organisms (species):

Leuciscus idus

Details on test organisms:

TEST ORGANISM
- Common name: Golden orfe
- Source: Fish farm Paul Eggers, 2354 Hohenwestedt, Germany
- Length at study initiation (length definition, mean, range and SD): 6.7 cm (range 6.0 - 7.2 cm)
- Weight at study initiation (mean and range, SD): 2.8 g (range 2.0 - 3.6 g)
- Method of breeding: oil-free aerated and charcoal filtered tap water, flow-through system Water temperature: 19 - 21 °C Duration of housing: about 3 months Mortality during the last 2 weeks of housing: 0.08 %; Medical treatment: Twice with 0.05 mg/l malachite green chloride, once with 10 mg/l tetracycline hydrochloride
Corpulence factor of the test fish batch: 0.9
- Feeding during test: 1 day before and during exposure.

ACCLIMATION
- Acclimation period: 3 days
- Type and amount of food: Growing feed F/B 50, ad libitum.
- Health during acclimation (any mortality observed): no mortality observed

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Hardness:

2.5 mmol/l

Test temperature:

20 - 21 °C

pH:

7.3 - 7.7

Dissolved oxygen:

7.8 - 8.6 mg/l

Nominal and measured concentrations:

Nominal test concentrations (mg/l):
4.64, 10, 21.5, 46.4, 100, control

Details on test conditions:

TEST SYSTEM
- Test vessel: glass aquaria (30 x 22 x 24 cm)
- Fill volume: 10 l
- Aeration: Continuous aeration with oil-free air
- No. of organisms per vessel: 10
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1
- Biomass loading rate: 2.8 g fish/l test water


TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: reconstituted freshwater according to DIN 38412, Part II, 1982; prepared from fully demineralised tap water (conductivity: max 10 micro MHO) by adding: 294.0 mg/l CaCl2 * 2 H2O 123.3 mg/l MgSO4 + 7 H2O 63.0 mg/l NaHCO3 5.5 mg/l KCl
- Ca/mg ratio: 4 : 1


OTHER TEST CONDITIONS
- Photoperiod: 16 : 8 hours day-night regime


EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Mortality and symptoms of intoxication after 1, 4, 24, 48, 72 and 96 hours

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

4.6 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC0

Effect conc.:

10 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

14.66 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

96 h

Dose descriptor:

LC100

Effect conc.:

21.5 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Results with reference substance (positive control):

48 h-LC50 of the positive control chloroacetamide: about 32 mg/l (corresponds to normal sensitivity).

Reported statistics and error estimates:

The LC50 value was calculated as the geometrical mean of LC0 (10 mg/l) and LC100 (21.5 mg7l) nominal values.

Sublethal observations / clinical signs:

During the 96 h exposure to citronellol, mortalities were as follows:

Nominal test / Cumulative mortality (%) after x hours
concentration / 1 / 4 / 24 / 48 / 72 / 96 /
(mg/l)
Control / 0 / 0 / 0 / 0 / 0 / 0 /
4.64 / 0 / 0 / 0 / 0 / 0 / 0 /
10.0 / 0 / 0 / 0 / 0 / 0 / 0 /
21.5 / 100 / 100 / 100 / 100 / 100 / 100 /
46.4 / 100 / 100 / 100 / 100 / 100 / 100 /
100.0 / 100 / 100 / 100 / 100 / 100 / 100 /

Symptoms of intoxication:

Nominal test / Symptoms of intoxication after x hours
concentration / 1 / 4 / 24 / 48 / 72 / 96 /
(mg/l)
Control / - / - / - / - / - / - /
4.64 / - / - / - / - / - / - /
10.0 / A / A / A / - / - / - /
21.5 / + / + / + / + / + / + /
46.4 / + / + / + / + / + / + /
100.0 / + / + / + / + / + / + /

Definitions of Symptoms:
-: No symptoms
A: Apathy
+: All fish dead

Chemical Analysis
No analytical dose-verification of the test item was carried out. Therefore all biological results refer to nominal test concentrations of Citronellol.

Description of key information

This endpoint was read across from Citronellol (3,7-dimethyl-6-Octen-1-ol, CAS 106 -22 -9).

A guideline study following German standard DIN 38 412, part L15 investigated the acute toxicity of citronellol to fish. Test fish of the species Leuciscus idus were exposed to Citronellol for 96 hours and a LC50 of 14.66 mg/l was determined at test termination (BASF AG, 1989). A second study tested the acute toxicity of the substance in Cyprinus auratus and detected a toxic threshold concentration of 8.6 mg/l after 1 hour (Binet, 1972).

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

14.66 mg/L