Methyl isonicotinate

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: as mentioned below

Principles of method if other than guideline:

Prediction is done using 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 (IUPAC name): Methyl Isonicotinate
- Molecular formula: C7H7NO2
- Molecular weight: 137.1373 g/mol
- Smiles notation: c1(C(=O)OC)ccncc1
- InChl: 1S/C7H7NO2/c1-10-7(9)6-2-4-8-5-3-6/h2-5H,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

Reference substance (positive control):

not specified

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

197.895 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" )  and ("d" and ( not "e") )  )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and "o" )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and "t" )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and ( not "ab") )  )  and "ac" )  and ("ad" and "ae" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acyl transfer via nucleophilic addition reaction OR Acylation >> Acyl transfer via nucleophilic addition reaction >> Isocyanates, Isothiocyanates  OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> N-Acylated heteroaromatic amines  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents  OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Phosphonates OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds OR SNAr >> Nucleophilic aromatic substitution on activated aryl and heteroaryl compounds >> Activated aryl and heteroaryl compounds by Protein binding by OASIS v1.3

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halo ethers by Protein binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinyl carboxamides (MA) by Protein binding potency

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "k"

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: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Halo Ester OR Surfactants-Nonionic by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Alkane branched with quaternary carbon OR Alkane, branched with tertiary carbon OR Alkene by Organic Functional groups

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Isopropyl by Organic Functional groups

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Biodegrades Fast by Biodeg probability (Biowin 1) ONLY

Domain logical expression index: "u"

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

Domain logical expression index: "v"

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 by DNA binding by OECD

Domain logical expression index: "w"

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

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Cycloalkene by Organic Functional groups

Domain logical expression index: "y"

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

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as tert-Butyl by Organic Functional groups

Domain logical expression index: "aa"

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 Aromatic Nitrogen AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Ester, aliphatic attach [-C(=O)O] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Pyridine, non fused rings  by Organic functional groups (US EPA)

Domain logical expression index: "ab"

Referential boundary: The target chemical should be classified as Pyridine Ester, 2-position  by Organic functional groups (US EPA)

Domain logical expression index: "ac"

Similarity boundary:Target: COC(=O)c1ccncc1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.398

Domain logical expression index: "ae"

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

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for Methyl Isonicotinate on Pseudokirchneriella subcapitata in a 72 hour study was estimated to be 197.89 mg/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 Methyl Isonicotinate (CAS no. 2459 -09 -8). EC50 value was estimated to be 197.89 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance Methyl Isonicotinate 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 (2017) 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 Methyl Isonicotinate (CAS no. 2459 -09 -8). EC50 value was estimated to be 197.89 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance Methyl Isonicotinate 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:

197.89 mg/L

Additional information

Various predicted data for the target chemical Methyl Isonicotinate (CAS No. 2459-09-8) and supporting weight of evidence studies for its read across substanceswere reviewed for toxicity to aquatic algae and cyanobacteria endpoint to summarize the following information:

 

Short term toxicity on aquatic algae and cyanobacteria of target chemical Methyl Isonicotinate (CAS No. 2459-09-8) is predicted using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances (2017).On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 197.89 mg/l for Pseudokirchneriella subcapitata for 72 duration. Based on this value it can be concluded that the substanceMethyl Isonicotinateis considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

In another prediction done using the EPI Suite ECOSAR version 1.10 (EPI Suite, 2017),the short term toxicity on green algae was predicted for test substance Methyl Isonicotinate (CAS: 2459 -09 -8). On the basis of effects observed in a static freshwater system, the effect concentration EC50 value for the substance is estimated to be 416.544 mg/l for green algae for 96 h duration. Based on this value, it can be concluded that the test chemical Methyl Isonicotinate can be considered as non-toxic to green algae at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

In a weight of evidencestudy from peer reviewed journal (G. Roderer, 1986) of the read across chemicalNiacinamide (CAS no. 98-92-0),short term toxicity to Poterbochromonas malhamensis study was carried out for 72 hrs. The study was based on the effects of the read across compound Niacinamide on Poterbochromonas malhamensis in a static fresh water system. Test chemical concentration used for the study was 5.5, 11 and 22 mg/l, respectively (nominal concentrations). The stock solution of test chemical was prepared in double distilled water. For test chemical tested, eight algal cultures (250 ml vol) were used which were divided into two groups with four cultures each: the control group (COC3) and the TriEL (Triethyl lead chloride) group (TO-T3). CO was the control culture without any added substance and TO was the one with 10µM TriEL only. The cultures C 1, C2, and C3 contained the protective agents i.e test chemical Niacinamide in the concentrations without TriEL being added, whereas Tl, T2, and T3 contained the same concentrations of the protective agents like Cl, C2, and C3, respectively, plus 10µM TriEL. Incubation was started with 0.1 X lo6 cells/ml (cf. arrowheads in the diagrams) and performed for 72 hr under standardized cultivation conditions. The cell densities were determined by counting the cells microscopically in a Thoma glass counting chamber. During this time the cell density of the control cultures (CO) increased up to 8 + 1 million cells/ml and that of the TriEL cultures (TO) decreased to 0.01-0.05 million cells/ml. For the present study about 800 algal cultures of 250 ml each were run. Numerous experiments were repeated as “blind” tests in order to check reproducibility. Based on effect on growth rate of the test organism Poterbochromonas malhamensis, the 72 hr EC0, value was determined to be 22 mg/l, respectively. Thus, based on the EC0 value, it can be concluded that the substance Niacinamide can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical Niacinamide can be considered as non-toxic to aquatic organisms and thus can considered to be not classified as per the CLP classification criteria.

 

For another read across chemicalNicotinic acid (CAS no. 59 -67 -6), short term toxicity to Scenedesmus subspicatus (green algae) study was carried out for 72 hrs (HSDB, 2016 and OECD SIDS, 1993). The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test) and other method DIN 38412L9, respectively. The study was based on the effects of the read across compound Nicotinic acid (CAS no. 59 -67 -6) on green algae in a static fresh water system. Test chemical concentration used for the study was in the range of 90 -100 mg/l. The growth inhibition was concentration and pH dependent. Based on effect on growth rate of the test organism green algae, the 72 hr EC0, EC10 and EbC50 value was determined to be 25, 30 and 90 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the substance Nicotinic acid can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical Nicotinic acid can be considered as non-toxic to aquatic organisms and thus can considered to be not classified as per the CLP classification criteria.

 

Thus, based on the overall reported results for target chemicalMethyl Isonicotinate(OECD QSAR toolbox version 3.3 and EPI suite, 2017) and for its read across substance (frompeer reviewed journal, authoritative database HSDB andsecondary source), it can be concluded that the test substanceMethyl Isonicotinatecan be considered asnon-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.