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EC number: 242-828-7 | CAS number: 19125-99-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Repeated dose toxicity: oral
The No Observed Adverse Effect
Level (NOAEL) for
2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione in rats is
estimated to be 994 mg/Kg bw/day after repeated exposure via oral route.
Repeated dose toxicity: inhalation
According
to Annex IX of the REACH regulation, testing by the inhalation route is
appropriate only if exposure of humans via inhalation is likely. Taking
into account the low vapour pressure of the substance
2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, which is
reported as 0.00000000141 Pa. Also considering the particle size
distribution of the substance the majority of the particles was found to
be in the size of 106 micrometer which is much larger size range
compared to the inhalable particulate matter. Thus, exposure to
inhalable dust, mist and vapour of the chemical
12-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is highly
unlikely. Therefore this study is considered for waiver.
Repeated dose toxicity: dermal
The
acute toxicity value for
2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione (as
provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the
use of the chemical; repeated exposure by the dermal route is unlikely
since the use of gloves is common practice in industries. Thus, it is
expected that
2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione shall not
exhibit 28 day repeated dose toxicity by the dermal route. In addition,
there is no data available that suggests that
2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione shall
exhibit repeated dose toxicity by the dermal route. Hence this end point
was considered for waiver.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: oral
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- 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
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Analytical verification of doses or concentrations:
- not specified
- Remarks:
- not specified
- Control animals:
- not specified
- Clinical signs:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 994 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: no significant changes were noted at mentioned dose level
- Critical effects observed:
- not specified
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione in rats is estimated to be 994 mg/Kg bw/day after repeated exposure via oral route.
- Executive summary:
Repeated dose oral toxicity was evaluated for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione using SSS QSAR prediction database. The study assumed the use of rats in a subacute study. Since no significant changes were noted, the No Observed Adverse Effect Level (NOAEL) for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is estimated to be 994 mg/Kg bw/day.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain logical expression:Result: In Domain
((((((("a"
or "b" or "c" or "d" or "e" )
and ("f"
and (
not "g")
)
)
and "h" )
and "i" )
and "j" )
and ("k"
and (
not "l")
)
)
and ("m"
and "n" )
)
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 Not categorized by Repeated dose
(HESS)
Domain
logical expression index: "g"
Referential
boundary: The
target chemical should be classified as Allyl esters (Hepatotoxicity)
Rank A OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank OR Valproic
acid (Hepatotoxicity) Alert by Repeated dose (HESS)
Domain
logical expression index: "h"
Similarity
boundary:Target:
CCCCNc1ccc2c3c1cccc3C(=O)N(CCCC)C2=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "i"
Similarity
boundary:Target:
CCCCNc1ccc2c3c1cccc3C(=O)N(CCCC)C2=O
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "j"
Similarity
boundary:Target:
CCCCNc1ccc2c3c1cccc3C(=O)N(CCCC)C2=O
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization
Domain
logical expression index: "k"
Referential
boundary: The
target chemical should be classified as H-acceptor-path3-H-acceptor by
in vivo mutagenicity (Micronucleus) alerts by ISS
Domain
logical expression index: "l"
Referential
boundary: The
target chemical should be classified as N-methylol derivatives by in
vivo mutagenicity (Micronucleus) alerts by ISS
Domain
logical expression index: "m"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= 0.722
Domain
logical expression index: "n"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 8.59
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 994 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is of K2 reliability and predicted from OECD QSAR toolbox.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Data waiving:
- other justification
- Justification for data waiving:
- other:
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: dermal
- Data waiving:
- other justification
- Justification for data waiving:
- other:
Reference
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity: oral
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 Repeated dose oral toxicity
endpoint and are represented here as weight of evidence approach:
Repeated dose oral toxicity was evaluated for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione using SSS QSAR prediction database. The study assumed the use of rats in a subacute study. Since no significant changes were noted, the No Observed Adverse Effect Level (NOAEL) for 2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is estimated to be 994 mg/Kg bw/day.
Groups of 10 rats /sex were fed structurally related substance 2-methyl-1H-isoindole-1,3(2H)-dione (CAS 550-77-4)at levels of 0, 0.25, 0.5 and 1.0% (as cited in HPVIS document). All rats were observed for mortality twice each day. Clinical signs and body weights were recorded at initiation and weekly thereafter. Food consumption was recorded weekly. After 30 days of treatment, all surviving rats were fasted overnight and weighed prior to terminal sacrifice and necropsy. At necropsy the liver and kidneys were weighed. The following tissues were saved from all animals: brain, pituitary, thoracic spinal cord, eyes, salivary glands (mandibular), stomach, trachea, thymus esophagus, heart, spleen, adrenals, pancreas, duodenum, jejunum, ileum, colon, cecum, mesenteric lymph node, urinary bladder, testes with epididymides and prostate (males), ovaries and uterus (females), femur, bone marrow (costochondral junction), lungs, liver, kidneys, thyroid (with parathyroids), skeletal muscle, and all gross lesions. Microscopic evaluation was conducted on sections of the lungs, liver, brain and kidneys from rats of all treatment groups. A necropsy also was performed on all rats that were sacrificed in extremis or were found dead during the study. One male rat in the 0.25% group died on Day 26 of the study. Statistically significant decreases in body weight of both male and female rats in the 0.5 and 1.0% groups (6% and 18% lower than controls for males and 4% and 11% lower than control for females, respectively) were noted during the fourth week of exposure. Mean food consumption values of the treated male and female rats were lower than control at some measurement periods, but the food consumption value for the male rats in the 1.0% group during the final week of exposure was the only statistically significant decrease noted. Mean compound consumption for the male rats in the 0.25, 0.50 and 1.0% groups ranged from 146 to 203 mg/kg/day, 330 to 403 mg/kg/day and 685 to 815 mg/kg/day, respectively. The mean compound consumption for the female rats in the 0.25, 0.5 and 1.0% groups range from 197 to 226 mg/kg/day, 409 to 573 mg/kg/day and 921 to 1100 mg/kg/day, respectively. The gross pathology revealed no treatment-related effects in any PI-treated group. Mean liver relative to terminal body weight was increased for both sexes and mean kidney weight relative to terminal body weight was increased for males at 1.0%. Microscopic evaluation revealed compound-related findings of centrilobular to diffuse hepatocellular enlargement in rats of both sexes in the 0.5 and 1.0% treatment groups. In addition, the severity of chronic progressive nephropathy was increased slightly in the male rats in the 1.0% group. There were no compound-related findings present in the tissues examined from the male or female rats in the 0.25% group. Thus, the No observed adverse effect level (NOAEL) for the substance2-methyl-1H-isoindole-1,3(2H)-dione is determined to be 250 mg/kg bw/day.
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 on Repeated exposure via oral route and is considered to not classified as per CLP regulation.
Repeated dose toxicity: inhalation
According
to Annex IX of the REACH regulation, testing by the inhalation route is
appropriate only if exposure of humans via inhalation is likely. Taking
into account the low vapour pressure of the substance
2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione, which is
reported as 0.00000000141 Pa. Also considering the particle size
distribution of the substance the majority of the particles was found to
be in the size of 106 micrometer which is much larger size range
compared to the inhalable particulate matter. Thus, exposure to
inhalable dust, mist and vapour of the chemical
12-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione is highly
unlikely. Therefore this study is considered for waiver.
Repeated dose toxicity: dermal
The
acute toxicity value for
2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione (as
provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the
use of the chemical; repeated exposure by the dermal route is unlikely
since the use of gloves is common practice in industries. Thus, it is
expected that
2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione shall not
exhibit 28 day repeated dose toxicity by the dermal route. In addition,
there is no data available that suggests that
2-butyl-6-(butylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione shall
exhibit repeated dose toxicity by the dermal route. Hence this end point
was considered for waiver.
Justification for classification or non-classification
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 on Repeated exposure via oral route and is considered to not classified as per CLP regulation.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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