Anisyl formate

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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 limited documentation / justification

Justification for type of information:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

The data is predicted using the OECD QSAR toolbox version 3.3 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: (4-methoxyphenyl)methyl formate
- Molecular formula: C9H10O3
- Molecular weight: 166.175 g/mol
- Smiles notation: c1(ccc(OC)cc1)COC=O
- InChl: 1S/C9H10O3/c1-11-9-4-2-8(3-5-9)6-12-7-10/h2-5,7H,6H2,1H3
- Substance type: Organic
- Physical state: Liquid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

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

Test type:

static

Water media type:

freshwater

Total exposure duration:

72 h

Test temperature:

21 deg.C

pH:

8.1

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

366.35 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

growth rate

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and "q" )  and ("r" and "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Carboxylic acid derivative AND Carboxylic acid ester AND Ether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkylarylether OR Aromatic compound OR Carboxylic acid derivative OR Carboxylic acid ester OR Ether by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Ester, aromatic attach [-C(=O)O] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] OR Oxygen, two olefinic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aryl OR Carboxylic acid ester OR Ether by Organic Functional groups ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  by Protein binding by OASIS v1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens OR Metalloids OR Rare Earth OR Transition Metals by Groups of elements

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid ester AND Ether AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Alkoxy OR Alkyl arenes OR Allyl OR Cycloalkene OR Fused carbocyclic aromatic OR Isopropyl OR Naphtalene OR No functional group found by Organic Functional groups (nested)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aromatic Carbon [C] AND Ester, aromatic attach [-C(=O)O] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Oxygen, two olefinic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Alkylarylether AND Aromatic compound AND Carboxylic acid derivative AND Carboxylic acid ester AND Ether by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.484

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.35

Validity criteria fulfilled:

not specified

Conclusions:

Using OECD QSAR toolbox version 3.3 the median Effective concentration (EC50) value for test chemical (4-methoxyphenyl)methyl formate on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 366.35 mg/L on the basis of effects on growth rate.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance (4-methoxyphenyl)methyl formate. EC50 value was estimated to be 366.35 mg/l for Pseudokirchneriella subcapitata for 72 h duration. This effect value indicating that the substance substance (4-methoxyphenyl)methyl formate (CAS no. 122-91-8) does not pose a significant hazard to algae and thus consider to be not classifies as per the CLP classification criteria.

Description of key information

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance (4-methoxyphenyl)methyl formate. EC50 value was estimated to be 366.35 mg/l for Pseudokirchneriella subcapitata for 72 h duration. This effect value indicating that the substance substance (4-methoxyphenyl)methyl formate (CAS no. 122-91-8) does not pose a significant hazard to algae and thus consider to be not classifies as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

366.35 mg/L

Additional information

Four studies including predicted data from validated tool and experimental data from secondary data source for toxicity to aquatic algae endpoint of test chemical (4-methoxyphenyl)methyl formate (Cas no. 122-91-8) with relevant read across which is close to target using log Kow as primary descriptor were summarised as follows:

 

First data from prediction using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, which indicate the short term toxicity on aquatic algae and cyanobacteria was predicted for target substance chemical (4-methoxyphenyl) methyl formate (Cas no. 122-91-8) . The EC50 value was estimated to be 366.35 mg/l for Pseudokirchneriella subcapitata for 72 h duration. 

Similarly prediction by EPI suite, ECOSAR version 1.1, on the basis of similarity of structure to chemicals for which the aquatic toxicity has been previously measured by structure-activity relationships (SARs) program suggest the EC50 value for toxicity on green algae was predicted. On the basis of EPI suite, ECOSAR version 1.1, the EC50 value for toxicity to green algae was predicted to be 106.737 mg/l for (4-methoxyphenyl) methyl formate in 96 hrs.

And read across 1,2-Dimethoxyethane (Cas no. 110-71-4) suggest Acute Toxicity To Aquatic algae (Selenastrum capricornutum) was performed according to OECD Guideline 201. In experiment Stock Solutions Prepared Approximately 1.0182 g of the chemical was brought to volume in a 100 ml volumetric flask with deionized water to prepare a stock concentration of 10,200 mg/L. The following amounts of stock (1.9, 3.75, 7.5, 15 and 30 ml) were used to make the test concentrations by mixing with 298.1, 296, 292.5, 285, and 270 ml of freshwater algal media individually.Analytical analysis performed by GC. Cell Counts Algal growth was measured by direct cell count using a 0.1mm deep hemacytometer under a compound microscope. Algal counts were conducted on day one and approximately every 24 hours thereafter. Morphological observations were also conducted on the test treatment using a compound microscope to detect abnormal cell morphology and coloration as compared to the control replicates. And EC50 values and their 95 percent confidence limits were estimated by a computer program (U.S. EPA, 1994) for calculating EC values by Probit analysis. Statistical differences were determined at a probability level of 0.05. Based on the experimental result the effect concentration (EC50) and No observed effect concentration (NOEC) of substance 1,2-Dimethoxyethane on test species Selenastrum capricornutum was observed to be >877 mg/l and 877 mg/l respectively on the basis of Growth Rate effect for 72 hrs exposure period. (Robust summary posted to the HPV Challenge Program sep. 27, 2000.)

From same data source i.e Robust summary posted to the HPV Challenge Program, 2002 for another read across chemical 1-methoxy-2-(2-methoxyethoxy)ethane (Cas no. 111-96-6) According to OECD Guideline 201 the effect concentation (EC10) of substance 1-methoxy-2-(2-methoxyethoxy)ethane on test species Scenedesmus subspicatus was observed to be >1000 mg/l on the basis of Growth Rate effect for 72 hrs exposure period.     

  

Thus based on the effects from all studies give the conclusion that test substance (4-methoxyphenyl) methyl formate (Cas no. 122-91-8) with effect concentrations in the range 106.737 to >1000 mg/l was likely to be non toxic to aquatic algae as it not meet the classification criteria of aquatic toxicity as per the CLP regulation.