Methyl isonicotinate

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: 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):

Daphnia magna

Test type:

static

Water media type:

freshwater

Total exposure duration:

48 h

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

334.579 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 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((("a" or "b" or "c" )  and "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "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 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 DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Sulfonylureas OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans 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 >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes 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 OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acid moiety OR Acrylamides OR Aliphatic Amines OR Amides OR Benzyl Nitriles OR Carbamate Esters OR Carbamate Esters, Phenyl OR Esters (phosphate) OR Esters, Monothiophosphates OR Halopyrdines OR Hydrazines OR Phenols OR Phenols, Poly OR Pyrazoles/Pyrroles OR Pyrethroids OR Salt OR Sulfonyl Ureas OR Surfactants-Anionic OR Thiocarbamates, Mono OR Thiocyanates OR Triazines, Aromatic OR Vinyl/Allyl Alcohols OR Vinyl/Allyl Esters OR Vinyl/Allyl Ethers OR Vinyl/Allyl Halides OR Vinyl/Allyl Ketones by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as 3-Methylcholantrene (Hepatotoxicity) Alert OR Phthalate esters (Testicular toxicity) Rank C by Repeated dose (HESS)

Domain logical expression index: "p"

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: "q"

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: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.229

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.29

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for Methyl Isonicotinate on Daphnia magna in a 48 hour study was estimated to be 334.57 mg/L on the basis of effects on intoxication

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 invertebrates was predicted for target substance Methyl Isonicotinate (CAS no. 2459 -09 -8). EC50 value was estimated to be 334.57 mg/l for Daphnia magna for 48 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 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for target substance Methyl Isonicotinate (CAS no. 2459 -09 -8). EC50 value was estimated to be 334.57 mg/l for Daphnia magna for 48 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

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

334.57 mg/L

Additional information

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

 

Short term toxicity on aquatic invertebrate of target chemicalMethyl 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 334.57 mg/l for Daphnia magna for 48 hr duration.

 

In another prediction done using the EPI Suite ECOSAR version 1.10 (EPI Suite, 2017), the short term toxicity on aquatic invertebrates was predicted for test substance Methyl Isonicotinate (CAS no. 2459 -09 -8). On the basis of effects observed in a static freshwater system, the lethal concentration LC50 value for the substance is estimated to be 939.938 mg/l for Daphnia magna for 48 duration.

 

Additional data was predicted using the ACD labs predicted median Lethal Concentration (LC50) of daphnia magna using v5.0.0.184. The value is supported by estimated Reliability Index (RI). Based on this, the LC50 value for test item Methyl Isonicotinate (CAS no. 2459 -09 -8) was predicted to be 150 mg/l for Daphnia magna.

 

In a supporting weight of evidence study from study report (ABITEC Report no. 380/17, study no. 93-60-7/SSS/2018, Sustainability Support Services (Europe) AB, 2017) of the read across chemical 3-Pyridinecarboxylic acid methyl ester (CAS no. 93-60-7),experimental study for inhibition of the mobility of daphnids was carried out with the read across chemical 3-Pyridinecarboxylic acid methyl ester according to OECD Guideline 202. The animals used for the test shall be less than 24 h old and should not be of first brood progeny. The stock solution (200 mg/L) was prepared by dissolving white powder in reconstituted water. Test solutions of required concentration were prepared by mixing the stock solution of the test sample with reconstituted test water. The test substance was tested at the concentration of 50, 70, 100, 140 and 200 mg/L, respectively. The test was performed under static conditions in fresh water system at 20±1°C temperature. Effects on immobilisation were observed for 48 hours. EC50 was calculated using non linear regression by the software Prism 4.0. The median effective concentration (EC50) for the test substance 3-Pyridinecarboxylic acid methyl ester (CAS no. 93-60-7) in Daphnia magna was determined to be 189.2 mg/L (95% CL: 140.4-254.9 mg/l) for immobilisation effects.

 

For the read across chemical Nicotinamide (CAS no. 98-92-0) from authoritative database (HSDB, 2016) and secondary source (IUCLID dataset, 2000), short term toxicity to aquatic invertebrates was performed in Daphnia magna for 24 hrs at > 1000 mg/l concentration based on immobilization. After test, the EC50 was determined to be >1000 mg/l for Nicotinamide (98 -92 -0) for daphnia magna for 24 hrs.

 

Thus, based on the overall reported results for target chemicalMethyl Isonicotinate(OECD QSAR toolbox version 3.3, EPI suite and ACD lab database, 2017) and for its read across substance (from study report,authoritative database HSDB andsecondary source),it can be concluded that the test substanceMethyl Isonicotinatecan be considered as non-toxic to aquatic environment and can be considered to be notclassified as per the CLP classification criteria.