Methyl isonicotinate

Endpoint summary

Description of key information

Short term toxicity to aquatic invertebrates

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.

Toxicity to aquatic algae and cyanobacteria

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.

Toxicity to micro-organisms

96 h toxicity test of substance methyl isonicotinate was conducted in Ciliate Tetrahymena pyriformis (T. WAYNE SCHULTZ et. al; 1985). Methyl Isonicotinate was diluted to 500 g/l with sterile distilled water . The study was performed in freshwater under static conditions at a temperature of 28°C.The amicronucleated strain GL-C of the common freshwater ciliate Tetrahymena pyriformis was reared in axenic culture at 28°C in a semidefined medium. Cultures were grown for 60 hr in 250-ml Erlenmeyer flasks containing 50 ml of test solution. Population growth and density were determined spectrophotometrically as absorbance at 540 mm. Each test chemical was assayed in duplicate for a minimum of three replicates using a five-step graded concentration series. Each replicate was assayed with freshly prepared stock solutions and flasks without test chemicals were used as controls.Population growth determinations were done using probit analysis in the Statistical Analysis System (SAS) software. For these data Y equals percentage control absorbance and X equals concentration (mg/liter). The 60-hr IGCso (50% growth inhibition concentration) and 95% confidence interval were determined and transformed to millimoles per liter for comparison. The goodness of fit was determined using the x2 value.The 60 hr EC50 value of test chemical methyl isonicotinate was determined to be 893.32 mg/l in Ciliate Tetrahymena pyriformis.

Additional information

Short term toxicity to aquatic invertebrates

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.

Toxicity to aquatic algae and cyanobacteria

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 (from peer reviewed journal, authoritative database HSDB andsecondary source), it can be concluded that the test substance Methyl Isonicotinate can be considered as non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Toxicity to micro-organisms

Various experimental studies for the target chemical Methyl Isonicotinate (CAS No. 2459-09-8)were reviewed for toxicity to micro-organism endpoint which are summarized as below:

 

In an experimental key study from peer reviewed journal (T. WAYNE SCHULTZ et. al; 1985), 96 h toxicity test of substance methyl isonicotinate was conducted in Ciliate Tetrahymena pyriformis. Methyl Isonicotinate was diluted to 500 g/l with sterile distilled water. The study was performed in freshwater under static conditions at a temperature of 28°C.The amicronucleated strain GL-C of the common freshwater ciliate Tetrahymena pyriformis was reared in axenic culture at 28°C in a semidefined medium. Cultures were grown for 60 hr in 250-ml Erlenmeyer flasks containing 50 ml of test solution. Population growth and density were determined spectrophotometrically as absorbance at 540 mm. Each test chemical was assayed in duplicate for a minimum of three replicates using a five-step graded concentration series. Each replicate was assayed with freshly prepared stock solutions and flasks without test chemicals were used as controls.Population growth determinations were done using probit analysis in the Statistical Analysis System (SAS) software. For these data Y equals percentage control absorbance and X equals concentration (mg/liter). The 60-hr IGCso (50% growth inhibition concentration) and 95% confidence interval were determined and transformed to millimoles per liter for comparison. The goodness of fit was determined using the x2 value. The 60 hr EC50 value of test chemical methyl isonicotinate was determined to be 893.32 mg/l in Ciliate Tetrahymena pyriformis.

 

Another aquatic toxicity study of micro-organism to the test substance Methyl Isonicotinate (CAS no. 2459-09-8) was conducted using Photobacterium phosphoreum, strain NRRL-B-11177 (also referred to as Vibrio fischerii, strain NRRL-B-11177) (Klaus L.E. Kaiser and Virginia S. Palabrica, 1991). The study was performed at a temperature of 15ᵒC and pH range 5 to 9, respectively. Recommneded reference substance that can be used for the study were Phenol and Sodium pentachlorophenate, respectively. When the test bacterium Photobacterium phosphoreum, strain NRRL-B-11177 was exposed to the test chemical Methyl Isonicotinate, reduction in light output was observed. Thus, based on this effect, the EC50 value during 5, 15 and 30 min exposure period was determined to be 198.235, 207.588 and 217.3669 mg/l, respectively.

 

Thus, based on the overall reported results for target chemical Methyl Isonicotinate, EC50 value ranges from198.235 to 893.32 mg/l, respectively.

On the basis of above mentioned available information for short term toxicity to aquatic invertebrates and toxicity to aquatic algae and cyanobacteria, test substance Methyl Isonicotinate can be considered as non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.