Anisyl formate

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

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):

Daphnia magna

Test type:

static

Water media type:

freshwater

Test temperature:

24 deg.C

pH:

7.9

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

124.05 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: Intoxication

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 6 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 ("o" and ( not "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 AN2 OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters 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 OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers 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 DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Phthalate esters (Testicular toxicity) Rank C OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding alerts for skin sensitization by OASIS v1.3

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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: "p"

Referential boundary: The target chemical should be classified as Triazine by Organic Functional groups (nested)

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 >= 0.779

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.23

Validity criteria fulfilled:

not specified

Conclusions:

The short term toxicity on Daphnia magna (aquatic invertebrates) was predicted for (4-methoxyphenyl)methyl formate using OECD QSAR toolbox version 3.3 and EC50 value was estimated to be 124.05 mg/l on Daphnia magna for 48 hrs duration considering Intoxication effects.

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 six closest read across substances, the short term toxicity on aquatic invertebrate was predicted for (4-methoxyphenyl)methyl formate (Cas no. 122-91-8). Effect concentration i.e EC50 value was estimated to be 124.05 mg/l for Daphnia magna for 48 hrs duration. Based on the effect value, (4-methoxyphenyl)methyl formate (Cas no. 122-91-8) was non toxic to aquatic invertebrates, hence it can be considered to be not classified  as per the CLP classification criteria for aquatic environment.

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 six closest read across substances, the short term toxicity on aquatic invertebrate was predicted for (4-methoxyphenyl)methyl formate (Cas no. 122-91-8). Effect concentration i.e EC50 value was estimated to be 124.05 mg/l for Daphnia magna for 48 hrs duration. Based on the effect value, (4-methoxyphenyl)methyl formate (Cas no. 122-91-8) was non toxic to aquatic invertebrates, hence it can be considered to be not classified  as per the CLP classification criteria for aquatic environment.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

124.05 mg/L

Additional information

Five studies including predicted data from validated tools and experimental data from authorative database for short term aquatic invertebrate’s 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 invertebrates was predicted for (4-methoxyphenyl) methyl formate (Cas no. 122-91-8) and the Effect concentration i.e EC50 value was estimated to be 124.05 mg/l for Daphnia magna for 48 hrs 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 LC50 value for short term toxicity to aquatic invertebrates was predicted. On the basis of EPI suite, ECOSAR version 1.1, the LC50 value for short term toxicity to aquatic invertebrates was predicted to be 166.009 mg/l for (4-methoxyphenyl) methyl formate in 48 hrs.

 

Above both predicted results of target assist by experimental result of read across chemical Methyl 4-acetamido-2-ethoxybenzoate i.e Ethopabate (Cas no. 59 -06 -3) authorative database i.e ECOTOX database indicate Short term toxicity to aquatic invertebrates was performed in Daphnia magna (Water Flea) for 48 hrs with <1 d age. Test in fresh water media with static condition. During the experiment, the EC50 value for Methyl 4-acetamido-2-ethoxybenzoate i.e Ethopabate (Cas no. 59 -06 -3) was determined to be 170 mg/l on the basis of mobility. 

 

Again from ECOTOX database for another read across Titanium Dioxide (Cas no. 13463-67-7) indicate short term toxicity to aquatic invertebrates was performed in Daphnia similis (Water Flea) for 48 hrs with <24 hr. (Neonate) age. Test in fresh water media with static condition and20 deg.C test temp., 7.2 to 7.8 pH, 40 to 48 mg/L CaCO3 hardness and ~ 160 uS/cm conductivity. During the experiment, the EC50 value for Titanium Dioxide (Cas no.13463-67-7) was observed to be 100 mg/l on the basis of mobility (based on the UV light effects).

 

And screening assessment by Ministers of the Environment and of Health Canada; June 2013 source for read across Carbon Black (Cas no. 1333-86-4) indicate The No effect concentration (NOEC) of substance carbon black (Cas no.1333-86-4) in test species Daphnia magna was observed to be 3200 mg/l on the basis of mobility effect.

Thus based on the all available effect and lethal concentrations which is in the range of 100 mg/l to 166.009 mg/l and No effect concentration (NOEC) 3200 mg/l for target and read across chemicals give the conclusion that test substance (4-methoxyphenyl) methyl formate (Cas no. 122-91-8) was likely to be non toxic to aquatic invertebrates as it not exceed the classification criteria, hence it can be considered to be not classified as per the CLP regulation.