2-Buten-1-ol, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-, (2E)-

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28/10/1998 to 25/3/1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

EPA OPPTS 850.5400 (Algal Toxicity, Tiers I and II) (January 2012)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Details on properties of test surrogate or analogue material (migrated information):
- Water solubility (under test conditions): 20 mg/L at 20°C

Analytical monitoring:

yes

Details on sampling:

- Concentrations: 0 (control and vehicle control), 0.65, 1.3, 2.5, 5, 10 mg a.i./L
- Sampling method: at 0-hour, 10 mL samples were collected from each parent solution. At 96-hours, composite samples were collected from each test substance and control treatment. The abiotic control flask was also sampled at this time. The 96-hours samples were centrifuged in glass culture tubes to remove the algal biomass. Samples at concentration below 0.300 mg/L were diluted with acetonitrile to a final concentration of 50%; samples above 0.65 mg/L were diluted in 80:20 acetonitrile: ABC reagent water (v:v) such that the concentration of analyte in the final extracts was within the range of the standard reference curve. Quality control fortifications samples (spikes) were prepared by spiking 10.0 mL of control water with Super Radjanol. Spikes were prepared at concentrations braketing the range of nominal concentrations of the test substance treatments. Samples and spikes were analysed by HPLC

Vehicle:

yes

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): DMF
- Concentration of vehicle in test medium (stock solution and final test solution(s) including control(s)): 100 µL/L
- Evidence of undissolved material (e.g. precipitate, surface film, etc): no evidence of undissolved material

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Details on test organisms:

TEST ORGANISM
- Common name: Selenastrum capricornatum
- Strain: 99-A5-SEL
- Source (laboratory, culture collection): Departement of Botany, Culture collection of algae, University of Texas, Austin
- Age of inoculum (at test initiation): 6 days old
- Method of cultivation: the parent stock of algae were received growing on an agar slant contained in a culture tube and was assigned ABC lot 98-1648-4. Periodically, new Selenastrum capricornatum culture was initiated using a portion of this parent stock or cloned for an existing culture derived from the parent stock in 100 mL of autoclaved culture medium.

ACCLIMATION
- Culturing media and conditions (same as test or not): same as test

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Test temperature:

22.4 to 22.9 °C at test initiation
23.4 to 24.3 °C at test termination
The test temperature was within the range specified in the protocol (24 ± 2°C)

pH:

7.5 to 7.6 at test initiation
8.4 to 8.7 at test termination

Nominal and measured concentrations:

Nominal concentrations: 0, 0.65, 1.3, 2.5, 5, 10 mg a.i/L
Measured concentrations (arithmetic means of T=0 and T=96h) : 0, 0.44, 0.8, 1.2, 2.6, 3.6 mg a.i/L

Details on test conditions:

TEST SYSTEM
- Test vessel: 250 ml Erlenmeyer flasks fitted with foam stoppers
- Type (delete if not applicable): closed
- Continuous agitation, agitation rate = 100 rpm
- Initial cells density: 1x104 cells/mL
- Control end cells density: 1.7x106 cells/mL
- No. of vessels per concentration (replicates): 3
- No. of vessels per control (replicates): 3
- No. of vessels per vehicle control (replicates): 3

GROWTH MEDIUM
- Standard medium used: yes

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: prepared in ABC reagent water which is defined as reverse osmosis/deionized water passed through carbon, ion exchange and organic adsorption cartridges and filtered through a 0.2 µm hollow fiber final filter to produce a 16-18 megaohms.cm water
- Metals: < 0.1 mg/L
- Pesticides: < 4 µL
- Chlorine: < 0.025 mg/L

OTHER TEST CONDITIONS
- Adjustment of pH: no adjustement
- Light intensity and quality: continuous cool white fluorescent lighting (4000 lux)

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
- Determination of cell concentrations: hematocytometer and Olympus Model BH-2 microscope

TEST CONCENTRATIONS
- Spacing factor for test concentrations: 2
- Range finding study
- Test concentrations: 0 (control and vehicle control), 0.1, 1, 10, 20 ,40 mg a.i/L
- Results used to determine the conditions for the definitive study: After 96 hours of incubation, percent decrease in cell density as compared to the vehicle control was 10, 76, 82 and 87% at 1, 10, 20 and 40 mg/L respectively. No cells were counted at 0.1 mg/L indicating a possible poor inoculation of this flask.

See table 1: Measured concentrations of Super Radjanol in media sampled during a 96-hour static test with the freshwater green alga, Selenastrum capricornatum

Reference substance (positive control):

no

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

2.5 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

act. ingr.

Basis for effect:

growth rate

Remarks on result:

other: 2.1-2.8 mg/L

Key result

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

0.44 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

act. ingr.

Basis for effect:

growth rate

See attached Table 1, 2, 3 and 4

Validity criteria fulfilled:

yes

Conclusions:

The 96-hour EC50 for Super Radjanol was estimated to be 2.5 mg a.i/L with 95% confidence limits of 2.1 and 2.8 mg/L
The NOEC was 0.44 mg a.i/L

Executive summary:

In a 96 hour toxicity study, the cultures of Selenastrum capricornatumwere exposed to Super radjanol at measured concentrations of 0 (control and vehicle control), 0.44, 0.80, 1.2, 2.6, 3.6 mg a.i./L under static conditions in accordance with the EPA OPPTS 850.5400 guideline. The EC₅₀  and NOEC values based on cell density were 2.5 and 0.44 mg a.i./L, respectively. The % growth inhibition in the treated algal culture as compared to the vehicle control ranged from 12 to 56.

 

There were no compound-related phytotoxic effects.

This toxicity study is considered as acceptable and satisfies with the guidelines requirements for freshwater green alga toxicity study.

Reference 2

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

0. INTRODUCTION:
The analogue approach is based on it's structural similarity, with the only difference being in the terminal ethyl group of the source chemical instead of the methyl of the target chemical (as defined in this dossier section number 1). The read-across is based in the hypothesis that this difference will not affect significantly the toxicity towards aquatic organisms. This approach is supported by the ECOSAR prediction of both the source and the target substances, showing similar toxicities among both substances, and to the experimental data on the source substance.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read read-across is from a source substance with the same functional groups than the target but only with a different alkyl chain (ethyl instead of methyl), which is believed not to have a significant effect on the properties of the substance.
The hydrolisys products are predicted to be the same except for the methyl group, which is not expected to affect significantly.
The mechanisms of action both products are predicted to be the same. The physical properties are also very similar, including it’s characteristic odour which is very similar in both cases.
About the trans/cis isomerism: in the source substance such ratio is unfortunately not specified in the report (the CAS number refers to the mixture of cis & trans) and in the target substance is typically 95% trans and 1% cis. However this possible difference is also not believed to have affect the toxicity towards aquatic organisms of the substance.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Both substances have a similar purity. In the source substance report, the purity is reported as 86.7%. In the target substance the typical purity content is 95%.

3. ANALOGUE APPROACH JUSTIFICATION
As can be seen in the data matrix detailed below, the physical properties of the target and source substances are very similar. As shown in the estimation results, in this case the differences in the water solubility and vapour pressure are not believed to have a relevant effect related to the toxicity to aquatic organisms.

4. DATA MATRIX
Appearance. Source substance: clear liquid at 20°C. Target substance: clear liquid at 20°C
Melting Point. Source substance: < - 20 °C. Target substance: < -20 °C
Boiling Point. Source substance: 279 °C. Target substance: 272 °C.
Relative density at 20°C. Source substance: 0.916 ± 0.001 Target substance: 0.921 ± 0.001
Vapour Pressure.
Source Substance: 1.71 * 10-2 Pa at 20°C; 4.24 * 10-2 Pa at 25°C.
Target Substance: 1.35* 10-01Pa at 20 °C; 2.08* 10-01Pa at °C.
Water Solubility. Source Substance: 25.83 mg/L at 20 °C. Target Substance: 59.36 at 20 °C

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Remarks:

QSAR on the same substance

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

> 1 - <= 10 mg/L

Remarks on result:

other:

Remarks:

derived from the read-across on the source substance together plus the QSAR prediction on the target substance

Key result

Duration:

96 h

Dose descriptor:

NOEC

Effect conc.:

0.44 mg/L

Remarks on result:

other:

Remarks:

NOEC from the study on the source substance, given here as worst case

Validity criteria fulfilled:

not applicable

Conclusions:

The EC50(96h) towards green algae on the registered substance is estimated to be in the range of 1 - 10 mg/L, based on a read across experimental study from a source substance plus a QSAR estimation on the target substance. For risk assessment purposes the EC50(96h) used is the result from the source substance study as worst case. EC50(96h) = 2.5 mg/L.
The NOEC(96) is estimated to be 0.44 mg/L, based on a read-across study from the source substance. The QSAR estimation does not provide NOEC results, and therefore the experimental value result from the source substance is used as a worst case.
For risk assessment purposes the EC50(96h) used is the result from the source substance study as worst case. EC50(96h) = 2.5 mg/L.

Reference 3

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2016-04-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
ECOSAR (ECOlogical Structure Activity Relationship), U.S. Environmental Protection Agency

2. MODEL (incl. version number)
V1.11 (July 24, 2012)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: C1(C)C(C)(C)C(CC=C(CC)CO)CC=1
Besides, the experimental water solubility (27.23 mg/L) and partition coefficient (4.3) have been introduced in the software and considered in the calculations.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Ecological Structure - Activity Relationships Program (ECOSAR) Methodology Document v1.11. The document describing the underlying methods uses to derive the estimation techniques and equations used in the ECOSAR model can be found at:
https://www.epa.gov/tsca-screening-tools/ecological-structure-activity-relationships-program-ecosar-methodology-document

5. APPLICABILITY DOMAIN
This substance is within the domain of the ECOSAR model based on its molecular weight (less than 1000 g/mol) and the log Kow (less than 6.4). Furthermore, the model can be suitable for chemicals class of neutral organic.

6. ADEQUACY OF THE RESULT
This method of estimation is reliable as its results are very similar to the experimental test results (ECOSAR: EC50=1,9 mg/L versus an Experimental EC50 = 2.5 mg/L). Furthermore, the estimated EC50 is more conservative (i.e. lower EC50) than the experimental. Therefore this estimation method is regarded as reliable and useful to be used to predict this property for this substance and for similar substances.

Reason / purpose for cross-reference:

read-across: supporting information

Remarks:

QSAR on the same substance

Qualifier:

according to guideline

Guideline:

other: ECHA Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals

Version / remarks:

May 2008

GLP compliance:

no

Remarks:

not applicable for a QSAR result

Specific details on test material used for the study:

Properties used for the calculation
- log Kow : 4.3 (experimental result)
- Water solubility : 25.8 mg/L (experimental result)

Test organisms (species):

other: Green algae

Details on test organisms:

No further details on the test organisms

Test type:

not specified

Total exposure duration:

96 h

Hardness:

no data

Test temperature:

no data

pH:

no data

Dissolved oxygen:

no data

Salinity:

no data

Conductivity:

no data

Nominal and measured concentrations:

not applicable

Reference substance (positive control):

not required

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

1.852 mg/L

Remarks on result:

other: ECOSAR Class: Neutral Organic SAR (Baseline toxicity)

Validity criteria fulfilled:

not applicable

Conclusions:

The toxicity to green algae has been estimated using the ECOSAR v1.11 (QSAR model from the U.S. EPA) for the substance 2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol. The result is EC50 after 96h = 1.9 mg/L
The substance falls within the applicability domain and therefore the predicted value can be considered reliable.

Executive summary:

The toxicity to green algae has been estimated using the ECOSAR v1.11 (QSAR model from the U.S. EPA) for the substance 2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol.

The result is EC50 after 96h = 1.9 mg/L (neutral organic SAR, baseline toxicity).

For the calculation, two experimental values of the same substance have been introduced to the model:

log Kow = 4.3

Water solubility = 25.8 mg/L

The substance falls within the applicability domain of the model

Reference 4

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2016-08-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
ECOSAR (ECOlogical Structure Activity Relationship), U.S. Environmental Protection Agency

2. MODEL (incl. version number)
V1.11 (July 24, 2012)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: C1(C)C(C)(C)C(CC=C(C)CO)CC=1
Besides, the experimental water solubility (59 mg/L) and partition coefficient (4.0) have been introduced in the software and considered in the calculations.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Ecological Structure - Activity Relationships Program (ECOSAR) Methodology Document v1.11. The document describing the underlying methods uses to derive the estimation techniques and equations used in the ECOSAR model can be found at:
https://www.epa.gov/tsca-screening-tools/ecological-structure-activity-relationships-program-ecosar-methodology-document

5. APPLICABILITY DOMAIN
This substance is within the domain of the ECOSAR model based on its molecular weight (less than 1000 g/mol) and the log Kow (less than 6.4). Furthermore, the model can be suitable for chemicals class of neutral organic.

6. ADEQUACY OF THE RESULT
As proved in the source substance (2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol ; EC number: 248-908-8; CAS number: 28219-61-6), this method of estimation is reliable as its results are are very similar to the experimental test results (ECOSAR: EC50=1,9 mg/L versus an Experimental EC50 = 2.5 mg/L). Furthermore, the estimated EC50 is more conservative (i.e. lower EC50) than the experimental.
Similarly, it can be expected that for the registered substance the same occurs: the estimation result is reliable and any possible difference between the calculated and experimental result would likely be in a more conservative outcome for the estimation result. Therefore the estimation result can be used as a reasonable worst case.
Concluding that the result of the estimation for the registered substance is regarded as reliable and useful to demonstrate the EC50 (48h) to green algae is in the range 1-10 mg/L.

Reason / purpose for cross-reference:

read-across: supporting information

Remarks:

QSAR with the same substance

Qualifier:

according to guideline

Guideline:

other: ECHA Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals

Version / remarks:

May 2008

GLP compliance:

no

Remarks:

not applicable for a QSAR result

Specific details on test material used for the study:

Properties used for the calculation
- log Kow: 4 (experimental result)
- Water solubility : 59 mg/L (experimental result)

Test organisms (species):

other: Green Algae

Details on test organisms:

No further details on the test organisms

Test type:

not specified

Total exposure duration:

96 h

Hardness:

no data

Test temperature:

no data

pH:

no data

Dissolved oxygen:

no data

Salinity:

no data

Conductivity:

no data

Nominal and measured concentrations:

not applicable

Details on test conditions:

no data

Reference substance (positive control):

not required

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

2.8 mg/L

Nominal / measured:

estimated

Basis for effect:

not specified

Validity criteria fulfilled:

not applicable

Conclusions:

The short term toxicity to daphnid has been estimated using the ECOSAR v1.11 for the registered substance
The result is EC50 after 96h = 2.8 mg/L

Executive summary:

The toxicity to green algae has been estimated using the ECOSAR v1.11 (QSAR model from the U.S. EPA) for the registered substance (target substance)

The result is EC50 after 96h = 2.8 mg/L (neutral organic SAR, baseline toxicity).

For the calculation, two experimental values of the same substance have been introduced to the model:

log Kow = 4.0

Water solubility = 59 mg/L

The substance falls within the applicability domain of the model

Description of key information

Three studies are available to evaluate the toxicity to aquatic algae:
1) Key Study on a similar substance: Experimental study, guideline EPA OPPTS 850.5400, performed under GLP conditions.
The test item is the substance 2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol (CAS 28219-61-6; EC 248-908-8).
Result is EC50(96h) = 2.5 mg/L, NOEC(96h)=0.4 mg/L
2) Supporting QSAR estimation on a similar substance: Estimation done with  ECOSAR v1.11 (QSAR model from the U.S. EPA)
The substance used for the calculation is 2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol (CAS 28219-61-6; EC 248-908-8).
Result is EC50(96h) = 1.9 mg/L
3) Supporting QSAR estimation on the substance under registration (i.e as defined in section 1 of this dossier).
Estimation done with  ECOSAR v1.11 (QSAR model from the U.S. EPA)
Result is EC50(96h) = 2.8 mg/L

Key value for chemical safety assessment

EC50 for freshwater algae:

2.5 mg/L

EC10 or NOEC for freshwater algae:

0.4 mg/L

Additional information

The toxicity towards aquatic algal EC50(96h) is estimated to be higher than 1 mg/L and the NOEC (96h) higher than 0.4 mg/L.

This toxic concentration estimation is based on a read-across from an experimental study conducted with a very similar similar substance (2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol ; EC number: 248-908 -8; CAS number: 28219-61-6) plus a QSAR estimation on the target substance. Both are giving similar and consistent results of EC50(96h) in the range of 1 -10 mg/L.

Besides, the read-across is supported with a QSAR estimation on the source substance, which gives very similar results to the experimental study, confirming the QSARs estimation for this endpoint and for this substances are reliable.

Further arguments supporting the validity of the read-across:

1) comparing the QSAR estimation of the source substance with the experimental result of the source substance: the estimated EC50 is slightly more conservative (i.e. lower EC50) than the experimental.

Similarly, it can be expected that for the target substance the same occurs: the estimation result is reliable and any possible difference between the calculated and experimental result would be in a more conservative outcome for the estimation result. Therefore the estimation result can be used as a reasonable worst case.

2) comparing the QSAR estimation of the source substance with the QSAR estimation of the target substance: the predicted EC50 is lower for the source substance. Therefore the target substance is expected to be less toxic than the source substance (i.e. EC50(96h) > 1,4 mg/L and NOEC (96h) > 0.4 mg/L)

For risk assessment purposes the EC50(96h) and the NOEC (96h) that will be used are the results from the source substance study as worst case.

.