Isononyl acetate

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 3.4 with logKow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material : 3,5,5-trimethylhexyl acetate
- Molecular formula : C11H22O2
- Molecular weight : 186.293 g/mol
- Smiles notation : C(C)(=O)OCCCCCCC(C)C
- InChl : 1S/C11H22O2/c1-10(2)8-6-4-5-7-9-13-11(3)12/h10H,4-9H2,1-3H3
- 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

Hardness:

285 mg CaCO3/L

Test temperature:

20 - 22 °C

pH:

7.6 - 7.7

Reference substance (positive control):

not specified

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

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

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 AN2 AND AN2 >> Shiff base formation after aldehyde release AND AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters AND SN1 AND SN1 >> Nucleophilic attack after carbenium ion formation AND SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters AND SN2 AND SN2 >> Acylation AND SN2 >> Acylation >> Specific Acetate Esters AND SN2 >> Nucleophilic substitution at sp3 Carbon atom AND SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

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 >> Formamides 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 Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones 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 >> Aromatic nitro 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 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Coumarins 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 Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, MW>500 by Estrogen Receptor Binding

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (Ka, pH 7)(Hydrowin) ONLY

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as 10 to 100 days by Hydrolysis half-life (Kb, pH 8)(Hydrowin) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Halogenated benzene (Nongenotox) by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as -CH-   [linear] AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Aliphatic alcohol  [-OH] by Bioaccumulation - metabolism alerts

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as -CH-   [linear] AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] by Bioaccumulation - metabolism alerts

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Alkyl substituent on aromatic ring by Bioaccumulation - metabolism alerts

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0747

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.35

Validity criteria fulfilled:

not specified

Conclusions:

The median Effective concentration (EC50) value for test chemical 3,5,5-trimethylhexyl acetate on Daphnia magna in a 48 hour study was estimated to be 116 mg/L on the basis of effects on intoxication

Executive summary:

Using the OECD QSAR toolbox version 3.4 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 3,5,5-trimethylhexyl acetate (CAS no. 40379 -24 -6). EC50 value was estimated to be 116 mg/l for Daphnia magna for 48 h duration. Based on this value it can be concluded that the substance 3,5,5-trimethylhexyl acetate 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 3.4 (2017) 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 3,5,5-trimethylhexyl acetate (CAS no. 40379 -24 -6). EC50 value was estimated to be 116 mg/l for Daphnia magna for 48 h duration. Based on this value it can be concluded that the substance 3,5,5-trimethylhexyl acetate 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:

116 mg/L

Additional information

Predicted data for the target chemical 3,5,5-trimethylhexyl acetate (CAS No. 40379-24-6) 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 chemical3,5,5-trimethylhexyl acetate (CAS No. 40379-24-6) is predicted using the OECD QSAR toolbox version 3.4 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 116 mg/l for Daphnia magna for 48 hr duration.Based on this value it can be concluded that the substance3,5,5-trimethylhexyl acetateis considered to be non-toxic to aquatic environment and can be considered to be not classified as per the CLP classification criteria.

 

In an another prediction done using the three different models i.e, Battery, Leadscope and SciQSAR present within Danish QSAR database, the short term toxicity on aquatic invertebrates was predicted for 3,5,5-trimethylhexyl acetate (CAS no. 40379 -24 -6). 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 3,5,5-trimethylhexyl acetate is estimated to be 594 mg/l for Daphnia magna during 48 hr exposure duration. Thus, on the basis of EC50 value, it can be concluded that the 3,5,5-trimethylhexyl acetate was likely to be non-toxic to aquatic invertebrates at environmentally relevant concentrations and can be considered not-classified as per the CLP classification criteria.

 

In a weight of evidencestudy from experimental study report (ABITEC, s.r.o., Sustainability Support Services (Europe) AB, Study no. 112-14-2/SSS/2018, 2017) of the read across chemical Octyl Acetate (CAS no. 112-14-1), determination of the inhibition of the mobility of daphnids was carried out with the read across substance Octyl Acetate according to OECD Guideline 202. The test substance was tested at the limit concentration of 100 mg/l. Effects on immobilisation and growth inhibition were observed for 48 hours. The effective concentration (EC8) for the test substance, Octyl Acetate in Daphnia magna was determined to be 100 mg/L for immobilisation and inhibition effects where 8% daphnia inhibited. As the EC8 was at 100 mg/l, thus EC50 was greater than 100 mg/l. So on that basis chemical Octyl Acetate was consider to be not toxic. This value indicates that the substance Octyl Acetate is likely to be non-hazardous to aquatic invertebrates and cannot be classified as toxic as per the CLP criteria.

 

For the read across chemical 3-methylbutyl 2-hydroxybenzoate (CAS no. 87-20-7) from peer reviewed journal (A.M. Api et. al; 2015), short term toxicity test to Daphnia magna was conducted to evaluate the effect of read across chemical 3-methylbutyl 2-hydroxybenzoate. 48 hrs short term toxicity test was conducted on Daphnia magna under static conditions. The 48 hr EC0 and EC100 value was determined to be 2 and 4 mg/l. The geometric mean was determined to be 2.8 mg/L. Thus, EC50 can be considered to be 2.8 mg/L. Based on the result the 3-methylbutyl 2-hydroxybenzoate can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical 3-methylbutyl 2-hydroxybenzoate can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

Another short term toxicity test was conducted on Daphnia magna for 24 hrs for the read across chemical 3-methylbutyl 2-hydroxybenzoate (CAS no. 87-20-7) (A.M. Api et. al; 2015). The study was based on the effect of the read across chemical 3-methylbutyl 2-hydroxybenzoate Daphnia magna on under static conditions. The 24 hrs EC50 value was determined to be 4.5 mg/L. Based on the EC50 value, the chemical 3-methylbutyl 2-hydroxybenzoate can be considered as toxic to aquatic organisms. Since the chemical is readily biodegradable in nature, chemical 3-methylbutyl 2-hydroxybenzoate can be considered as non-toxic to aquatic organisms and thus can be considered to be not classified as per the CLP classification criteria.

 

Thus, based on the overall reported results for target chemical3,5,5-trimethylhexyl acetate(OECD QSAR toolbox version 3.3 and Danish QSAR database, 2017) and for its read across substance (fromstudy report and peer reviewed journal),it can be concluded that the test substance3,5,5-trimethylhexyl acetatecan be considered as non-toxic to aquatic environment and can be considered to be notclassified as per the CLP classification criteria.