p-tolyl acetate

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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:

no guideline available

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3 with log Kow as the primary descriptor.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 4-methylphenyl acetate
- Molecular formula: C9H10O2
- Molecular weight: 150.176 g/mol
- Smiles notation: c1(ccc(C)cc1)OC(C)=O
- InChI: 1S/C9H10O2/c1-7-3-5-9(6-4-7)11-8(2)10/h3-6H,1-2H3
- Substance type: Organic
- Physical state: Liquid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Danio rerio (previous name: Brachydanio rerio)

Test type:

static

Water media type:

freshwater

Total exposure duration:

96 h

Test temperature:

25 degC

pH:

6.9

Reference substance (positive control):

not specified

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

122.09 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Sublethal observations / clinical signs:

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 8 nearest neighbours
Domain  logical expression:Result: In Domain

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

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.1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis or thiolysis AND Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  by Protein binding by OASIS v1.3

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Class 3 (unspecific reactivity) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "f"

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

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 Class 3 (unspecific reactivity) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acyl halides (Genotox) OR Aliphatic azo and azoxy (Genotox) OR Aliphatic halogens (Genotox) OR Aliphatic N-nitro group (Genotox) OR alpha,beta-unsaturated carbonyls (Genotox) OR Benzenesulfonic ethers, methylation (Nongenotox) OR Epoxides and aziridines (Genotox) OR Halogenated benzene (Nongenotox) OR Hydrazine (Genotox) OR Imidazole, benzimidazole (Nongenotox) OR Nitro-aromatic (Genotox) OR Primary aromatic amine,hydroxyl amine and its derived esters (Genotox) OR Simple aldehyde (Genotox) OR Steroidal estrogens (nongenotoxic & genotoxic) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity OR Structural alerts for both genotoxic and nongenotoxic carcinogenicity OR Substituted n-alkylcarboxylic acids (Nongenotox) OR Substituted phenoxyacid (Nongenotox) OR Trichloro (or fluoro) ethylene and Tetrachloro (or fluoro) ethylene (Nongenotox)  by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives by DNA alerts for AMES, MN and CA by OASIS v.1.3

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 Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "p"

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

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Cyclo conjugated system by Organic Functional groups

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as Fused carbocyclic aromatic by Organic Functional groups

Domain logical expression index: "x"

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

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Oxyphenistain (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "z"

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

Domain logical expression index: "aa"

Referential boundary: The target chemical should be classified as Allyl esters (Hepatotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "ab"

Similarity boundary:Target: Cc1ccc(OC(C)=O)cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "ac"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.0453

Domain logical expression index: "ad"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.76

Validity criteria fulfilled:

not specified

Conclusions:

The median lethal concentration (LC50) for the test substance, p-tolyl acetate, in Danio rerio on the basis of mortality effect was estimated to be 122.09 mg/L.

Executive summary:

A study was predicted using OECD QSAR toolbox version 3.3 (2017); to assess the toxicity effect of p-tolyl acetate on fish in a 96 hours of exposure. The median lethal concentration (LC50) for the test substance, p-tolyl acetate, in Danio rerio on the basis of mortality effect was estimated to be 122.09 mg/L. Thus, on the basis of this LC50 value and according to CLP Criteria for aquatic classification of the substance, it is concluded that p-tolyl acetate (CAS no. 140-39-6) does not exhibit short term toxicity to fish.

Description of key information

A study was predicted using OECD QSAR toolbox version 3.3 (2017); to assess the toxicity effect of p-tolyl acetate on fish in a 96 hours of exposure. The median lethal concentration (LC50) for the test substance, p-tolyl acetate, in Danio rerio on the basis of mortality effect was estimated to be 122.09 mg/L. Thus, on the basis of this LC50 value and according to CLP Criteria for aquatic classification of the substance, it is concluded that p-tolyl acetate (CAS no. 140-39-6) does not exhibit short term toxicity to fish.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

122.09 mg/L

Additional information

Various studies including experimental data and predicted results from validated model for toxicity to fish with the target substance p-tolyl acetate (CAS No.140-39-6) and to its read across substance methyl acetate (Cas no. 79-20-9) by considering its structure-activity relationships, were summarized as follows:

 

A study was predicted using OECD QSAR toolbox version 3.3 (2017); to assess the toxicity effect of p-tolyl acetate on fish in a 96 hours of exposure. The median lethal concentration (LC50) for the test substance, p-tolyl acetate, in Danio rerio on the basis of mortality effect was estimated to be 122.09 mg/L.

 

Also, based on the Ecological Structure Activity Relationships (ECOSAR) Predictive Model version 1.11(2017), the median lethal concentration (LC50) for the test substance, p-tolyl acetate, in fish was estimated to be 92.914 mg/L on the basis of mortality effect in a 96 hour study.  But the BCF value of p-tolyl acetate was not >= 500 as well as the substance was found to be readily bio-degradable in water compartment. 

 

Experimental result (United States department of the interior fish and wildlife service; March 1957) for target chemical p-tolyl acetate (140-39-6) indicate that the short term toxicity test was performed on fish Petromyzon marinus at 5 mg/l concentration for 24 hrs. The fish was treated and maintained in good laboratory conditions. The pH was at 7.5-8.2 and temperature was maintained at 20 degree C.After experiment it was noted that the no mortality was observed thus no observed effect concentration (NOEC) for short term toxicity to fish Petromyzon marinus,Salmo gairdnerii and Lepomis macrochious for p-tolyl acetate (CAS No.-140-39-6) was consider to be NOEC at 5 mg/l concentration.

 

Another data from experimental study (Center for Lake Superior Environmental Studies, University of Wisconsin, Superior, WI:326 p.; 1985) for read across chemical Methyl acetate (Cas no. 79-20-9) indicates that in preliminary assessment of acute fish toxicity of test substance Methyl acetate was conducted in a static freshwater system for 96 hrs. on fish species Pimephales promelas of 32 days age with 18.6 MM length and 0.103 G weight. The test concentrations used for the study was 0, 439, 548, 685, 857 and 1070 mg/l. During experiment the gas liquid chromatography was used for analytical detection. For data analysis the LC50 with corresponding 95% confidence intervals were calculated using the corrected average of analyzed tank concentration and the Trimmed Spearman-Karber Method used. On the basis of behaviour effect the lethal concentration for test substance methyl acetate was found to be 399 mg/l.

 

In an additional experimental study (ECOTOX database;2017) for same read across substance i.e methyl acetate (Cas no. 79-20-9) on fish Pimephales promelas was carried out for 24 hr, the lethal concentration i.e LC50 was noted to be 96 h LC50 = 320 mg/L on the basis of mortality effect in static freshwater study condition.

 

So, based on the above predicted and experimental studies for substance p-tolyl acetate(CAS No. 140-39-6) and to its read across substance methyl acetate (CAS No. 79-20-9), the lethal concentration (LC50) was found to be in the range of 92.914mg/L to 399mg/L and NOEC value to be 5 mg/L.Based on the LC50 value the substance may classify for aquatic classification, but the BCF value of p-tolyl acetate was not >= 500 as well as the substance was found to be readily bio-degradable in water compartment. Thus, according to CLP Criteria for aquatic classification of the substance, it is concluded that p-tolyl acetate (CAS no. 140-39-6) does not exhibit short term toxicity to fish.