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

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

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]: 736 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:

Prediction using OECD QSAR Toolbox 3.3.

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:

This was a reproductive study performed in two parts. In the first part, males were treated for 70 to 90 days with 0 (1mL of distilled water), 750, 1500, or 3000 mg/kg/day of undiluted JP-8 jet fuel, then mated to untreated females (one female at a time).

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-triazi ne-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-triazi ne-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
CAS 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

Administration / exposure

Route of administration:

oral: unspecified

Type of inhalation exposure (if applicable):

not specified

Vehicle:

not specified

Details on exposure:

No data available

Details on mating procedure:

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:

90 days

Frequency of treatment:

Daily

Details on study schedule:

No data available

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 750, 1500, or 3000 mg/kg/day
Basis:
nominal conc.

No. of animals per sex per dose:

11

Control animals:

not specified

Details on study design:

No data available

Positive control:

No data available

Examinations

Parental animals: Observations and examinations:

No data available

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

No data available

Postmortem examinations (parental animals):

No data available

Postmortem examinations (offspring):

No data available

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not specified

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Mortality / viability:

not specified

Body weight and weight changes:

not specified

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not specified

Histopathological findings:

not examined

Overall reproductive toxicity

Reproductive 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 "f" )  )

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"

Parametric boundary:The target chemical should have a value of log Kow which is >= 10

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 18

Applicant's summary and conclusion

Conclusions:

Since no compound related effects were observed, 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 736 mg/kg bw/day (actual dose received)

Executive summary:

The reproductive 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 Toolbox version 3.3

Since no compound related effects were observed, 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 736 mg/kg bw/day (actual dose received)