Nonan-2-one

Endpoint summary

Description of key information

Short-term toxicity to fish:

Short term toxicity study of test chemical2-Nonanoneto Fathead Minnow (Pimephales promelas) was carried out for 96 hrs.

 

The objective of this study was to develop procedures that relate modes of acute toxic action in the fathead minnow (Pimephales promelas) to chemical structures and properties. An empirically derived database for diverse chemical structures of acute toxicity and corresponding modes of toxic action was developed through joint toxic action studies, the establishment of toxicodynamic profiles, and behavioral and dose–response interpretation of 96-h LC50 tests.

 

Chemicals in the fathead minnow database were evaluated through analyses of dose–response relationships and behavioral responses associated with 96-h LC50 bioassays. Based on the amount of available information for a test compound, a level of confidence was assigned to a mode of action determination.

 

28 - 30 d old juveline test organisms were used for the study. The test was performed under flowthrough condition with temp. of 25 ± 1°C.

 

Test was conducted using Lake Superior water at 25±1°C.Aqueous toxicant concentrations were measured in tests with quality assurance criteria requiring 80% agreement between duplicate samples and 90 to 110% spike recovery. Flow-through exposures were conducted using cycling proportional, modified Benoit, or electronic diluters. Tests conducted which were conducted on the Benoit and electronic diluters did not have replicate tank exposures.

Median lethal concentration (LC50) was calculated using the Trimmed Spearman–Karber Method, with 95% confidence intervals being calculated when possible.

 

The change of LC50 values over time (LC50 ratio) and the ratio of measured 96-h LC50 values to those predicted from a baseline narcosis (narcosis I) QSAR were used as supportive data for assessing potential modes of action. Each mode of action classification was assigned a level of confidence based on the type of data used when making the assessment; confidence levels were high (Level A using FATS and joint toxic action data), moderate (Level B using behavior syndrome, LC50 ratios, Te values, and structural similarity to Level A compounds), and low (Level C using behavioral comments, concentration/response slope, and structural similarity within a chemical class).

 

Thus, the mode of action for the test chemical was Narcosis I: Level B confidence alongwithtype 1 behaviour syndrome. Test organism had showed depressed locomotor activity with little or no response to outside stimuli. Body coloration became darker with most fish dying within 24 h.

 

Based on mortality, the 96 hr LC50 value for Fathead Minnow (Pimephales promelas) was found to be 15.2 mg/l.These experimental lethal concentration suggest that test chemical2-Nonanone is toxic to fish and thus classified in aquatic category 3 as per the CLP criteria.

Short term toxicity to aquatic invertebrates

Based on the prediction done 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 fornonan-2-one (CAS No.821-55-6). EC50 value was estimated to be 235.99mg/L on the basis of intoxication for Daphnia magna for 48 hrs duration. Based on this value it can be concluded that thenonan-2-one (CAS No.821-55-6) was considered to be not classified to aquatic invertebrates as per the CLP regulations.

Toxicity to aquatic algae and cyanobacteria

Based on the prediction done 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 2-Nonanone (CAS no. 821 -55 -6) (2017). EC50 value was estimated to be 152.5 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance 2-Nonanone is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

Additional information

Short-term toxicity to fish:

Four different studies which includes two experimental from peer reviewed journal and study report and remaining two from validated predicted model for short term fish toxicity endpoint for target chemical 2-Nonanone (Cas no. 821-55-6) are summarized as followed:

First experimental study suggest Short term toxicity study of test chemical 2-Nonanone to Fathead Minnow (Pimephales promelas) was carried out for 96 hrs. The objective of this study was to develop procedures that relate modes of acute toxic action in the fathead minnow (Pimephales promelas) to chemical structures and properties. An empirically derived database for diverse chemical structures of acute toxicity and corresponding modes of toxic action was developed through joint toxic action studies, the establishment of toxicodynamic profiles, and behavioral and dose–response interpretation of 96-h LC50 tests.Chemicals in the fathead minnow database were evaluated through analyses of dose–response relationships and behavioral responses associated with 96-h LC50 bioassays. Based on the amount of available information for a test compound, a level of confidence was assigned to a mode of action determination.28 - 30 d old juveline test organisms were used for the study. The test was performed under flowthrough condition with temp. of 25 ± 1°C.

Median lethal concentration (LC50) was calculated using the Trimmed Spearman–Karber Method, with 95% confidence intervals being calculated when possible. The change of LC50 values over time (LC50 ratio) and the ratio of measured 96-h LC50 values to those predicted from a baseline narcosis (narcosis I) QSAR were used as supportive data for assessing potential modes of action. Each mode of action classification was assigned a level of confidence based on the type of data used when making the assessment; confidence levels were high (Level A using FATS and joint toxic action data), moderate (Level B using behavior syndrome, LC50 ratios, Te values, and structural similarity to Level A compounds), and low (Level C using behavioral comments, concentration/response slope, and structural similarity within a chemical class). Thus, the mode of action for the test chemical was Narcosis I: Level B confidence alongwithtype 1 behaviour syndrome. Test organism had showed depressed locomotor activity with little or no response to outside stimuli. Body coloration became darker with most fish dying within 24 h. Based on mortality, the 96 hr LC50 value for Fathead Minnow (Pimephales promelas) was found to be 15.2 mg/l.This experimental lethal concentration suggest that test chemical 2-Nonanone is toxic to fish and thus classified in aquatic category 3 as per the CLP criteria.

Other Experimental study give assistance to above experimental result i.e the short term toxicity study was conducted to test the effect of 2 - nonanone on fathead minnows in a flow through conditions. The nominal concentration used were 0, 7.67, 11.8, 18.1, 27.8, or 42.8 mg/L.Affected fish lost schooling behaviour, swam near tank bottom, and were hypoactive. Fish were darkly colored, had increased respiration, and lost equilibrium prior to death. Mortalities at 96 hrs: 27.8 mg/L 20/20; 42.8 mg/L, 20/20. No mortalities at lower concentrations.

Therefore LC50 of 2-nonanone in fathead minnows in a flow-through system was found to be 15.2 mg/L for 96 hour.

Lethal concentration by Predicted database Danish QSAR (Database developed by National Food Institute, Technical University of Denmark, with support from the Danish Environmental Protection Agency, the Nordic Council of Ministers and the European Chemicals Agency, 2017) indicate based on mortality, the estimated 96 hrs LC50 value by three different model i.e, Battery, Leadscope and SciQSAR used within Danish QSAR database was found to be 13.194 mg/l.

And another predicted model by EPI Suite ECOSAR version 1.10 indicate the 96 hours LC50 was estimated to be 26.825 mg/l on Fish for substance 2-Nonanone (CAS no.821-55-6) on the basis of mortality effects. 

Above all experimental and predicted values for median lethal dose concentration(LC50) is in the range of 13.194 -26.825 mg/l conclude the target chemical 2-Nonanone (Cas no. 821-55-6) is is toxic to fish and thus classified in aquatic category 3 as per the CLP criteria.

Short term toxicity to aquatic invertebrates

Short term toxicity to aquatic invertebrates was summaries for nonan-2-one (CAS No.821-55-6) from one predicted QSAR report and its read-across substances2-butanone (78-93-3) and Pentanol (71-41-0), both having 50-60% structural similarity with target were reviewed to summarize the following information:

 

Based on the prediction done 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 fornonan-2-one (CAS No.821-55-6). EC50 value was estimated to be 235.99mg/L on the basis of intoxication for Daphnia magna for 48 hrs duration.

 

Short term toxicity to aquatic invertebrates was performed according to the OECD guideline 202 on read across substance 2-butanone (78-93-3) having 50-60% structural similarity with target (J-check, Environment Agency ,Ministry of Health, Labour and Welfare,Ministry of Economy, Trade and Industry, and Ministry of the Environment, 2010) in daphnia magna for 48 hrs. Number of organism per vessel are 5 in static test type at 20 degree C. Nominal concentration of 1000 mg/l and control were taken. Other test conditions like room light at 16 hours light and 8 hours dark was taken. After the experiment, the EC 50 value for 2-butanone (78-93-3) for daphnia magna was determined to be >1000 mg/l. Based on the value, 2-butanone (78-93-3) was considered to be non-toxic to aquatic invertebrates and can be considered as not classified as per the CLP regulations.

 

Another read across Pentanol (71-41-0) has also taken having 50-60% structural similarity with target (Ecotox database, U.S Environmental Protection Agency,2017)Short term toxicity to aquatic invertebrates was performed in 5 Daphnia at static test type for 24 hrs. After the 24 hrs, the EC 0 and EC 100 value for Pentanol (71-41-0) for daphnia magna was determined to be 208 and 800 mg/l on the basis of behavior. Based on the value, Pentanol was considered to be non-toxic to aquatic invertebrates and can be considered to be not classified as per the CLP regulations.

On the basis of results for toxicity to aquatic invertebrates from target, read across chemical 2-butanone (78-93-3) and Pentanol (71-41-0), both having 50-60% structural similarity with target,as both the read across substances had value greater than 100 mg/l has supported the classification of target.

Thus,based on the above predictions and studies it can be considered that nonan-2-one (CAS No.821-55-6) can be considered to be non-toxic to aquatic invertebrates and can be considered to be not classified as per the criteria of CLP regulation.

Toxicity to aquatic algae and cyanobacteria

In different studies, 2 -nonanone has been investigated for toxicity to aquatic algae and cyanobacteria. These include1 predicted datafor the target chemical 2-Nonanone (CAS No. 821 -55 -6)which is supported further by 2 studies (1 study from authoritative database and 1 study from secondary source) for its closest read across substance with log Kow as the primary descriptor.

In a prediction done 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 2-Nonanone (CAS no. 821 -55 -6) (2017). EC50 value was estimated to be 152.5 mg/l for Pseudokirchneriella subcapitata for 72 h duration. Based on this value it can be concluded that the substance 2-Nonanone is considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

Weight of evidence study of read across substance2 -butanone (CAS no. 78-93-3) to green algae was carried out for 72 hrs(J-CHECK, 2016). The study was

based on the effects of the read across compound 2 -butanone (CAS no. 78-93-3) on green algae in a static fresh water system. Based on effect on growth rate of the test organism green algae, the 72 hr EC50 and NOEC value was determined to be 1200 and 93 mg/l, respectively and on the basis of areas under the growth curves, the 72 hr EC50 and NOEC value was determined to be 570 and 98 mg/l, respectively. Thus, based on the EC50 value, it can be concluded that the read across substance 2 -butanone can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP classification criteria.

 

Another short term toxicity to Pseudokirchnerella subcapitata (algae) study of the read across compound 2 -heptanone (CAS no. 110-43-0)was carried out for

72 hrs(Eastman Chemical Company, 2007). The study was performed according to OECD Guideline 201 (Alga, Growth Inhibition Test). The study was based on the effects of the read across compound 2 -heptanone (CAS no. 110-43-0) on Pseudokirchnerella subcapitata in a static fresh water system at an average temperature of 24 °C and pH of 7.3 -7.7, respectively under constantly illumination of light with intensity of 741 +/- 1.7 foot-candles. Test chemical conc. used for the study were 12.5, 25, 50, 100 and 200 mg/l (nominal concentrations) and 6.2, 11.9, 22.1, 42.7, 86.3 mg/L(measured concentrations), respectively. Based on the effect on cell concentrations and growth rate of test organism Pseudokirchneriella subcapitata, the 72 hr ErC50, EbC50 and NOEC was determined to be 98.2 mg/L, 75.5 and 42.7 mg/L respectively for 2 -heptanone. Thus, based on EC50value, it can be concluded that the substance 2 -heptanone can be considered as toxic to aquatic organisms. Since the chemical 2 -heptanone is readily biodegradable in nature, chemical 2-heptanone can be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP classification criteria.

 

Based on the overall reported results for target chemical2-Nonanone(study 1 OECD QSAR toolbox version 3.3, 2017) and for its read across substance (study 2 and 3 from J-CHECK authoritative database and secondary source), it can be concluded that the test substance2 -Nonanonecan be considered as non-toxic to aquatic organisms and thus cannot be classified as hazardous as per the CLP classification criteria.

 

Toxicity to microorganisms:

Four different studies all includes experimental from peer reviewed journal for toxicity to micro organism endpoint for target chemical 2-Nonanone (Cas no. 821-55-6) are summarized as followed:

First experimental study suggest toxicity to micro-organisms study was conducted on Tetrahymena pyriformis for 48 hrs.Stock solutions of test chemical was prepared in dimethyl sulfoxide (DMSO) at conc. of 2.5, 5, 10, 25 or 50 mg/l. The volume of stock solution added to each test flask did not exceed 0.35 ml, an amount that does not alter Tetrahymena population growth.Test chemical was tested in a range-finder prior to testing in duplicate for three additional replicates. Each replicate was set up using freshly prepared stock solutions.

 

After 48 hrs of exposure duration of test organism to test chemical 2-nonanone,population density was measured spectrophotometrically at 540 nm.The 50 percent growth inhibitory concentration, IGC50, was determined using Probit Analysis of Statistical Analysis System (SAS) software with as the absorbency normalized as percentage of control and X as the toxicant concentration in parts per million. Based on growth inhibition of test organism, the IGC50 value was found to be 449 mg/l.

Another experimental study indicates the effects of 2 nonanone on Tetrahymena pyriformis was conducted under static condition. The test was allowed to run through 8-9 cell cycles. Semi defined proteose-peptone-based medium were inoculated to a density of 2500 cells/ml with log-growth-phase ciliates in the presence of the test material in DMSO. The test material was evaluated in each of three replicates at 6-8 different concentrations. Controls were inoculated with T. pyriformis in the absence of test material. Following incubation at 27 C, the population density of T. pyriformis was measured at 540 nM. The 50% growth inhibitory concentration was determined from probit analysis of absorbance values andconcentrations.IGC50 was found to be 33.26 mg/L under static condition for 2-Nonanone for 50% growth inhibition of Tetrahymena pyriformis.

And other experiment suggest In Toxicity to microorganisms study for 2-Nonanone was observed for Penicillium digitatum FRR 1562 and Colletotrichum musae DAR 24962.The MIC of each of the volatiles was evaluated and compound was classified as germicidal or germistatic in its effect on decay microorganisms. Agermicidal effect is the death of a microorganism, whereas a germ static effect is the inhibition of microbial replication). The agar disks of decay microorganisms which failed to grow due to the MIC of the compound were transferred onto new agar media free from the tested volatile and incubated for a further 5 days at 25 °C.The MIC observed with respect to 2 nonanone in Penicillium digitatum FRR 1562 was found to be 4.82 mmol/dish and for Colletotrichum musae DAR 24962 was found to be 3.58 mmol/dish.

And last experimental result suggest The 10 days toxicity study was conducted to evaluated to inhibitory effects of 2 nonanone.Erwinia carotovora UNSW 031700 was used as a test organism exposed to the concentration of 1.5ml/dish The NOEC was found to be 1.5m/dish for Erwinia carotovora.

Above all experimental values for Inhibition growth concentration (IGC50) and minimum inhibition concentration (MIC) conclude the target chemical 2-Nonanone (Cas no. 821-55-6) has no concern for toxicity to micro organism for acute exposure.