Pentyl 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:

Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary descriptors.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): Pentyl formate
- Molecular formula: C6H12O2
- Molecular weight: 116.158 g/mole
- 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

Hardness:

No data

Test temperature:

24 deg.C

pH:

No data

Dissolved oxygen:

No data

Salinity:

No data

Conductivity:

No data

Nominal and measured concentrations:

No data

Details on test conditions:

No data

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

111.61 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" or "e" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and "n" )  and "o" )  and ("p" and ( not "q") )  )  and "r" )  and "s" )  and ("t" and ( not "u") )  )  and "v" )  and "w" )  and ("x" and "y" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Formic acid and formates by OECD HPV Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones 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 Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 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 SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates 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 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR 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 >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes 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 (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by DPRA Cysteine peptide depletion

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as High reactive OR High reactive >> Activated haloarenes OR High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds OR Low reactive OR Low reactive >> Alicyclic ketones by DPRA Cysteine peptide depletion

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Class 3 (unspecific reactivity) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Halo Ester OR Schiff Bases-Azomethine OR Surfactants-Nonionic OR Vinyl/Allyl Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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: "u"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "v"

Similarity boundary:Target: CCCCCOC=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "w"

Similarity boundary:Target: CCCCCOC=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.738

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.83

Validity criteria fulfilled:

not specified

Conclusions:

Using OECD QSAR toolbox version 3.3 the median Effective concentration (EC50) value for test chemical Pentyl formate on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 111.61mg/L on the basis of effects on growth rate.

Executive summary:

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 Pentyl formate (CAS no. 638-49-3). EC50 value was estimated to be 111.61 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance Pentyl formate (CAS no. 638-49-3) is considered to be non toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Description of key information

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 Pentyl formate (CAS no. 638-49-3). EC50 value was estimated to be 111.61 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance Pentyl formate (CAS no. 638-49-3) is considered to be non toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Key value for chemical safety assessment

EC50 for freshwater algae:

111.61 mg/L

Additional information

Four studies including predicted data from validated tools and experimental data from authorative database for toxicity to aquatic algae endpoint of test chemical Pentyl formate (Cas no. 638-49-3) with relevant read across which is close to target by structure were summarised as follows:

 

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 Pentyl formate (Cas no. 638-49-3).The EC50 value was estimated to be 111.61mg/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 on the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 56.39 mg/l for green algae for 96 h duration.

 

Also prediction for target by Danish QSAR database indicate using the three different models i.e, Battery, Leadscope and SciQSAR within Danish QSAR database, the short term toxicity on green algae was predicted for test substance Pentyl formate (Cas no. 638-49-3). The average EC50 value was given by the third model i.e, Battery model. On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance Pentyl formate is estimated to be 26.21 mg/l for Pseudokirchneriella subcapitata during 72 hr exposure duration. 

 

Last study from experimental data of read across chemical Butyl acetate (Cas no. 123-86-4) from ECOTOX authoritative database, 2017 indicate short term toxicity to green algae species Chlorococcales (Green Algae Order) study was carried out for 24 hrs. The study was based on the effects of the test compound Butyl acetate (CAS no. 1306 -38 -3) on Chlorococcales sp. in a static fresh water system. Based on effect on Physiology (Assimilation efficiency) of the test organism Anabaena sp. the 24 hr EC50 value was observed to be 1200 mg/l.

Thus based on the all predicted effect concentrations of target which is in the range 26.21 mg/l to 111.61mg/l of target give the conclusion that the test chemical Pentyl formate (Cas no. 638-49-3) can be considered as toxic to aquatic environment as per ECOSAR and Danish QSAR database , Since the chemical is readily biodegradable in nature, chemical Pentyl formate can be considered as non-toxic to algae at environmentally relevant concentrations this aquatic classification of target supported by read across chemical with effect value (LC50) 1200 mg/l and thus overall chemical Pentyl formate (Cas no. 638-49-3) considered to be not-classified as per the CLP classification criteria.