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

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed in accordance to EU-guidelines, however a chemical analysis of the test substance in the test medium was not carried out. Additionally, the study is non-GLP.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: EU Directive 79/831/EEC, Annex V, part C.

GLP compliance:

no

Analytical monitoring:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method The highest test concentration (100 mg/l, nominal) of the test substance was prepared using both of Tween 80 (100 mg/l) and dilution water. The stock dispersion was stirred at 20 °C for 1020 min. Following this serial dilutions of this test solution were made in order to obtain the additional desired test concentrations. 10 ml of the specific dilution was added per test vessel.

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Source: Daphnia magna Straus, originally obtained from the Institute National de Recherche Chimique Appliquee, France and cultured in the laboratories of BASF since 1978.
- Age at study initiation (mean and range, SD): 2 - 24 hours

ACCLIMATION
- Type and amount of food: 1 x daily grown Green algae culture

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Hardness:

2.70 +/- 0.5 mmol/l

Test temperature:

19 - 21 °C

pH:

7.8 - 8.1

Dissolved oxygen:

6.3 - 9.4 mg/l

Nominal and measured concentrations:

Nominal test concentrations (mg/l):
0.78, 1.56, 3.12, 6.24, 12.5, 25.0, 49.9, 100.0 and a control

Details on test conditions:

TEST SYSTEM
- Test vessel: flat bottom glass tubes
- Fill volume: 10 ml
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4


TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: according to the test guideline DIN 38412, L 11
- Ca/mg ratio: 4 :1
Acidity constant - PH 4.3: 0.80 +/- 9.1 mmol/l
Molar ratio: Na:K ca. 10 :1

OTHER TEST CONDITIONS
- Photoperiod: 16 : 8 hours day-night regime
- Light intensity: diffuse light (5 microeinstein/m*m*s) at 400 - 750 nm wave length


EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Mobility after 0, 3, 6, 24, 48 h

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

3.1 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC0

Effect conc.:

6.24 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

17.48 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC100

Effect conc.:

49.9 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Reported statistics and error estimates:

The EC50 was determined using the moving average procedure according to Thompson (1947).

Nominal 
test          /   Cumulative immobilization of daphnia (%) concentration  /   after x hours
(mg/l)        /   0 /   3 /   6 /  24 /  48 /
Control       /   0 /   0 /   0 /   0 /   0 /
  0.78        /   0 /   0 /   0 /   0 /   0 /
  1.56        /   0 /   0 /   0 /   0 /   0 /
  3.12        /   0 /   0 /   0 /   0 /   0 /
  6.24        /   0 /   0 /   0 /   0 /   0 /
 12.5         /   0 /   5 /   5 /   5 /   5 /
 25.0         /   0 /   5 /  45 /  70 /  80 /
 49.9         /   0 / 100 / 100 / 100 / 100 /
100.0         /   0 / 100 / 100 / 100 / 100 /


EC50 (48 h): 17.48 mg/l (CL 95 %: 14.94 - 20.02 mg/l).
EC0 (48 h): 6.24 mg/l
EC100 (48 h): 49.9 mg/l

EC50 (24 h): 20.87 mg/l (CL 95 %: 16.3 - 25.44 mg/l).
EC0 (24 h): 12.5 mg/l
EC100 (24 h): 49.9 mg/l

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 2

Endpoint:

short-term toxicity to aquatic invertebrates

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: The study was performed in accordance to EU-guidelines, however a chemical analysis of the test substance in the test medium was not carried out. Additionally, the study is non-GLP.

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: EU Directive 79/831/EEC, Annex V, part C.

GLP compliance:

no

Analytical monitoring:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method The highest test concentration (100 mg/l, nominal) of the test substance was prepared using both of Tween 80 (100 mg/l) and dilution water. The stock dispersion was stirred at 20 °C for 1020 min. Following this serial dilutions of this test solution were made in order to obtain the additional desired test concentrations. 10 ml of the specific dilution was added per test vessel.

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Source: Daphnia magna Straus, originally obtained from the Institute National de Recherche Chimique Appliquee, France and cultured in the laboratories of BASF since 1978.
- Age at study initiation (mean and range, SD): 2 - 24 hours

ACCLIMATION
- Type and amount of food: 1 x daily grown Green algae culture

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Hardness:

2.70 +/- 0.5 mmol/l

Test temperature:

19 - 21 °C

pH:

7.8 - 8.1

Dissolved oxygen:

6.3 - 9.4 mg/l

Nominal and measured concentrations:

Nominal test concentrations (mg/l):
0.78, 1.56, 3.12, 6.24, 12.5, 25.0, 49.9, 100.0 and a control

Details on test conditions:

TEST SYSTEM
- Test vessel: flat bottom glass tubes
- Fill volume: 10 ml
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4


TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: according to the test guideline DIN 38412, L 11
- Ca/mg ratio: 4 :1
Acidity constant - PH 4.3: 0.80 +/- 9.1 mmol/l
Molar ratio: Na:K ca. 10 :1

OTHER TEST CONDITIONS
- Photoperiod: 16 : 8 hours day-night regime
- Light intensity: diffuse light (5 microeinstein/m*m*s) at 400 - 750 nm wave length


EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Mobility after 0, 3, 6, 24, 48 h

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

3.1 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC0

Effect conc.:

6.24 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

17.48 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC100

Effect conc.:

49.9 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Reported statistics and error estimates:

The EC50 was determined using the moving average procedure according to Thompson (1947).

Nominal 
test          /   Cumulative immobilization of daphnia (%) concentration  /   after x hours
(mg/l)        /   0 /   3 /   6 /  24 /  48 /
Control       /   0 /   0 /   0 /   0 /   0 /
  0.78        /   0 /   0 /   0 /   0 /   0 /
  1.56        /   0 /   0 /   0 /   0 /   0 /
  3.12        /   0 /   0 /   0 /   0 /   0 /
  6.24        /   0 /   0 /   0 /   0 /   0 /
 12.5         /   0 /   5 /   5 /   5 /   5 /
 25.0         /   0 /   5 /  45 /  70 /  80 /
 49.9         /   0 / 100 / 100 / 100 / 100 /
100.0         /   0 / 100 / 100 / 100 / 100 /


EC50 (48 h): 17.48 mg/l (CL 95 %: 14.94 - 20.02 mg/l).
EC0 (48 h): 6.24 mg/l
EC100 (48 h): 49.9 mg/l

EC50 (24 h): 20.87 mg/l (CL 95 %: 16.3 - 25.44 mg/l).
EC0 (24 h): 12.5 mg/l
EC100 (24 h): 49.9 mg/l

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.

One guideline study on the toxicity of Citronellol to Daphnia magna is available. Employing a static test system set up according to EU Directive 79/831/EEC, Annex V, part C an EC50 of 17.48 mg/l was determined after 48 hours (BASF AG, 1989).

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

17.48 mg/L