Butane-1,2,3,4-tetracarboxylic acid

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:

Data is from OECD QSAR toolbox version.3.3 and 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 QSAR Toolbox version 3.3 with log kow as the primary discriptors.

GLP compliance:

no

Specific details on test material used for the study:

-Name of test material: Butane-1,2,3,4-tetracarboxylic acid-Molecular formula: C8H10O8-Molecular weight: 234.160 g/mol-Smiles notation : C(C(C(CC(=O)O)C(=O)O)C(=O)O)C(=O)O- InChl (if other than submission substance): InChI=1S/C8H10O8/c9-5(10)1-3(7(13)14)4(8(15)16)2-6(11)12/h3-4H,1-2H2,(H,9,10)(H,11,12)(H,13,14)(H,15,16)- Substance type: Organic-Physical Appearance: Solid

Analytical monitoring:

not specified

Vehicle:

not specified

Test organisms (species):

Daphnia magna

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

445.82 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 6 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 ( not "j") )  )  and "k" )  and "l" )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and "t" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Carboxylic acid by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acid, aliphatic attach [-COOH] AND Alcohol, olefinic attach [-OH] AND Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Carbonyl, aliphatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Multi alcohol  AND Olefinic carbon [=CH- or =C<] AND Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Carbonic acid derivative AND Carboxylic acid AND Carboxylic acid derivative by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> N-methylol derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrobiphenyls and Bridged Nitrobiphenyls OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.3

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 >> Benzylamines-Acylation OR Michael addition 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 >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR SN1 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 >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Alkali Earth OR Halogens OR Metals OR Transition Metals by Groups of elements

Domain logical expression index: "o"

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: "p"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 15 - Phosphorus P OR Group 16 - Selennm Se OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Carboxylic acids (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.74

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.649

Conclusions:

The effective concentration EC50 value for Butane-1,2,3,4-tetracarboxylic acid (Cas no.1703-58-8), in Daphnia magna (aquatic invertebrates) in 48 hrs study was predicted using OECD QSAR toolbox version 3.3 and EC50 value was estimated to be 445.8 mg/l considering Intoxication effects. Based on the obtained value, it can be concluded that the Butane-1,2,3,4-tetracarboxylic acid (Cas no.1703-58-8) is non-toxic to Daphnia magna.

Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrates was predicted for Butane-1,2,3,4-tetracarboxylic acid (Cas no.1703-58-8). Effect concentration i.e EC50 value was estimated to be 445.8 mg/l for Daphnia magna for 48 hrs duration. It was concluded that the Butane-1,2,3,4-tetracarboxylic acid (Cas no.1703-58-8) was likely to be non-toxic to aquatic invertebrates, hence it can be considered to be classified as per the CLP classification criteria for aquatic environment.

Description of key information

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrates was predicted for Butane-1,2,3,4-tetracarboxylic acid (Cas no.1703-58-8). Effect concentration i.e EC50 value was estimated to be 445.8 mg/l for Daphnia magna for 48 hrs duration. It was concluded that the Butane-1,2,3,4-tetracarboxylic acid (Cas no.1703-58-8) was likely to be non-toxic to aquatic invertebrates, hence it can be considered to be classified as per the CLP classification criteria for aquatic environment.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

445.8 mg/L

Additional information

Four studies including predicted data from validated tools and experimental data from peer reviewed journal and authorative database for short term aquatic invertebrate’s endpoint of test chemical Butane-1,2,3,4-tetracarboxylic acid (Cas no. 1703-58-8) with relevant read across which is close to target using log Kow as primary descriptor were summarised as follows:

 

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the short term toxicity on aquatic invertebrates was predicted for Butane-1,2,3,4-tetracarboxylic acid (Cas no.1703-58-8). Effect concentration i.e EC50 value was estimated to be 445.8 mg/l for Daphnia magna for 48 hrs duration.

 

Similar prediction byUsing the EPI Suite ECOSAR version 1.11, the short term toxicity on fish was predicted for Butane-1,2,3,4-tetracarboxylic acid (CAS no. 1703-58-8) the effects observed in a freshwater system. The lethal concentration LC50 value for Butane-1,2,3,4-tetracarboxylic acid estimated to be 20500000 mg/l for fish for 96 hr exposure duration.

 

 

Above predicted results of target assist by experimental result of read across chemicalL-(+)-lactic acid(Cas no:79-33-4) from peer reviewed journalChemosphere 1998, In a 48-h short term toxicity test, 5 Daphnia magna were exposed to L-(+)-lactic acid at nominal concentrations of 0 (control), 320 and 560 mg/L under static conditions. The Effective concentration to 50% of Daphnia magna is 240 mg/l at which the organisms were immobile.

 

One another read across (Malonic acid)(Cas no.141-82-2) fromJournal of the Water Pollution Control Federation,1980. The effective concentration EC50 value forDaphnia magna when exposed to Malonic acid for 48 Hour is275 mg/l. on the basis of obtained value it can be concluded that the Malonic acid is not toxic toDaphnia magna.

 

Thus based on the all available effect concentrations which is in the range of 240 mg/l to 20500000 mg/l for target and read across chemicals which come to the conclusion that test substance Butane-1,2,3,4-tetracarboxylic acid (Cas no. 1703-58-8) was likely to be non-toxic to aquatic algae as it not exceed the classification criteria, hence it can be considered to be not classified as per the CLP regulation.