2-butyl-6-(butylamino)-1H-benz[de]isoquinoline-1,3(2H)-dione

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:

Data is predicted by OECD QSAR Toolbox version 3.4. The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Data is predicted by OECD QSAR Toolbox version 3.4.

GLP compliance:

not specified

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

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

172.247 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 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "d" or "e" )  and "f" )  and ("g" and ( not "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 "u" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Imides (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN1 AND SN1 >> Alkylation after metabolically formed carbenium ion species AND SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives AND SN2 AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation AND SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Secondary aromatic amine by DNA binding by OECD

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 Imides by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "f"

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: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Phenol Amines OR Phenols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not Related to an Existing ECOSAR Class by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as SHOULD NOT BE PROFILED by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Moderate by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aromatic N-acyl amine (Genotox) OR Halogenated benzene (Nongenotox) OR Quinones (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Thiocarbamates/Sulfides (Hepatotoxicity) No rank by Repeated dose (HESS)

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.5

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 8.21

Validity criteria fulfilled:

not specified

Conclusions:

The Lethal concentration (LC50) value for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione on Danio rerio (previous name: Brachydanio rerio) in a 96 hrs. study was estimated to be 172.24 mg/L on the basis of effects on mortality in static freshwater.

Executive summary:

The toxic effects of the test compound 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione were predicted using QSAR toolbox

version 3.4. The prediction was based on the effects of the test compound on Danio rerio (previous name: Brachydanio rerio) in a static fresh water system during a 96 hour exposure. The Lethal concentration (LC50) value was estimated to be 172.24 mg/L on the basis of effects on mortality. Thus, based on this value, test chemical 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione can be considered as non-toxic to fish and thus can be considered to be not classified as per the CLP classification criteria.

Description of key information

The Lethal concentration (LC50) value for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione on Danio rerio (previous name: Brachydanio rerio) in a 96 hrs. study was estimated to be 172.24 mg/L on the basis of effects on mortality in static freshwater by OECD QSAR toolbox.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

172.24 mg/L

Additional information

Short term toxicity to fish:
Predicted data for the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione and its read across substance were reviewed for short term toxicity to fish endpoint and are represented here as weight of evidence approach:

The toxic effects of the test compound 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione were predicted using QSAR toolbox version 3.4. The prediction was based on the effects of the test compound on Danio rerio (previous name: Brachydanio rerio) in a static fresh water system during a 96 hour exposure. The Lethal concentration (LC50) value was estimated to be 172.24 mg/L on the basis of effects on mortality.

96 hour short term toxicity to fish was carried for the substance 2-methyl-1H-isoindole-1,3(2H)-dione (CAS 550-77-4)according to OECD guideline 203 (HPVIS database, 2017). The test species used was fresh water Oncorhynchus mykiss in static condition. Nominal concentrations used were 0, 40, 68,116, 200, 293.3 mg/L while measured concentrations were 0, 34.6, 58.7, 100.3, 174.6, 293.3 mg/L. LC50 were calculated at 24, 48, 72, and 96 h. At test termination (96-hour exposure), all fish appeared normal in the control.  As per the observations made, the 50% Lethal concentration value of the substance 2-methyl-1H-isoindole-1,3(2H)-dione to Oncorhynchus mykiss is determined to be 110 mg/L.

Considering above data and by applying weight of evidence approach it can be concluded that the substance 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is not toxic to fish and is considered to not classified as per CLP regulation.