bis(2-ethylhexyl) 4,4’-{6-[4-tert-butylcarbamoyl)anilino]-1,3,5-triazine-2,4-diyldiimino}dibenzoate

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from QSAR Toolbox Version 3.3

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other: Predicted data

Title:

[R]: 622 mg/kg bw/day (actual dose received); Estimation for NOAEL for CAS 154702-15-5

Author:

Sustainability Support Services (Europe) AB

Year:

2015

Bibliographic source:

SSS QSAR Prediction Team

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: The prediction is done using QSAR Toolbox version 3.3

Principles of method if other than guideline:

Dose range-finding study performed to determine the appropriate dose levels for a combined repeated dose toxicity study with reproduction/developmental toxicity screening test according to OECD guideline 422. As far as possible, the study was performed in

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

421-450-8

EC Name:

-

Cas Number:

154702-15-5

Molecular formula:

C44H59N7O5

IUPAC Name:

Bis(2-ethylhexyl) 4,4’-{6-[4-tert-butylcarbamoyl)anilino]-1,3,5-triazine-2,4-diyldiimino}dibenzoate

Constituent 2

Reference substance name:

benzoic acid, 4,4'-[[6-[[4-[[(1,1-dimethylethyl)amino]carbonyl]phenyl]amino]-1,3,5-triazin e-2,4-diyl]diimino]bis-, 1,1'-bis(2-ethylhexyl) ester

IUPAC Name:

benzoic acid, 4,4'-[[6-[[4-[[(1,1-dimethylethyl)amino]carbonyl]phenyl]amino]-1,3,5-triazin e-2,4-diyl]diimino]bis-, 1,1'-bis(2-ethylhexyl) ester

Details on test material:

CAS No.: 154702-15-5
EC No.: 421-450-8
Substance Name: benzoic acid, 4,4'-[[6-[[4-[[(1,1-dimethylethyl)amino]carbonyl]phenyl]amino]-1,3,5-triazine-2,4-diyl]diimino]bis-, 1,1'-bis(2-ethylhexyl) ester
SMILES:CCCCC(CC)COC(=O)c1ccc(Nc2nc(Nc3ccc(C(=O)NC(C)(C)C)cc3)nc(Nc3ccc(C(=O)OCC(CC)CCCC)cc3)n2)cc1

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No Data Available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

No Data Available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No Data Available

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
148, 622, 1100 mg/kg bw/day (actual dose received)
Basis:
no data

No. of animals per sex per dose:

No data available

Control animals:

not specified

Details on study design:

No data available

Positive control:

No data available

Examinations

Observations and examinations performed and frequency:

No data available

Sacrifice and pathology:

No data available

Other examinations:

No data available

Statistics:

No data available

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

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

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

621.8 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Non-covalent interaction AND Non-covalent interaction >> DNA intercalation AND Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain by DNA binding by OASIS v.1.3

Domain logical expression index: "b"

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

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Ester aminolysis AND Acylation >> Ester aminolysis >> Amides by Protein binding by OASIS v1.3

Domain logical expression index: "d"

Similarity boundary:Target: CCCCC(CC)COC(=O)c1ccc(Nc2nc(Nc3ccc(C(=O)NC(C)(C)C)cc3)nc(Nc3ccc(C(=O)OCC(CC)CCCC)cc3)n2)cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as 1,2-diol OR Alcohol OR Alkyl fluoride OR Alkyl halide OR Alkylthiol OR Amine OR Anion OR Aryl chloride OR Aryl halide OR Azo compound OR Carbamic acid ester (uretane) OR Carboxylic acid OR Carboxylic acid salt OR Cation OR CO2 derivative (general) OR Dialkylether OR Ether OR Halogen derivative OR Heterocyclic compound OR Hydroxy compound OR Lactone OR No functional group found OR Phenol OR Primary alcohol OR Primary aliphatic amine OR Primary amine OR Quaternary ammonium salt OR Secondary alcohol OR Secondary aliphatic amine OR Secondary amine OR Sulfonic acid OR Sulfonic acid derivative OR Tertiary aliphatic amine OR Tertiary amine OR Tertiary mixed amine OR Thioether OR Thiol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "h"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.81

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 20.5

Applicant's summary and conclusion

Conclusions:

The no observed adverse effect level (NOAEL) for test material benzoic acid, 4,4'-[[6-[[4-[[(1,1-dimethylethyl)amino]carbonyl]phenyl]amino]-1,3,5-triazine-2,4-diyl]diimino]bis-,1,1'-bis(2-ethylhexyl) ester in rats was found to be 621.799987793 mg/kg bw/day (actual dose received)

Executive summary:

The repeated dose toxicity of benzoic acid, 4,4'-[[6-[[4-[[(1,1-dimethylethyl)amino]carbonyl]phenyl]amino]-1,3,5-triazine-2,4-diyl]diimino]bis-,1,1'-bis(2-ethylhexyl) ester to rats was estimated using QSAR Toolboox version 3.3

The no observed adverse effect level (NOAEL) for test material benzoic acid, 4,4'-[[6-[[4-[[(1,1-dimethylethyl)amino]carbonyl]phenyl]amino]-1,3,5-triazine-2,4-diyl]diimino]bis-,1,1'-bis(2-ethylhexyl) ester in rats was found to be 621.799987793 mg/kg bw/day (actual dose received)