p,p',p''-tris(diethylamino)trityl alcohol

Endpoint summary

Description of key information

4-(Diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)benzenemethanol is not likely to be toxic upon repeated oral exposure by oral route.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

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:

The supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: Prediction is done using QSAR Toolbox version 3.4

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material: p,p',p''-tris(diethylamino)trityl alcohol
- Molecular formula: C31H43N3O
- Molecular weight: 473.701 g/mol
- Smiles notation: OC(c1ccc(N(CC)CC)cc1)(c1ccc(N(CC)CC)cc1)c1ccc(N(CC)CC)cc1
- Substance type: Organic

Species:

rat

Strain:

Wistar

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: gavage

Details on route of administration:

not specified

Vehicle:

not specified

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

not specified

Frequency of treatment:

not specified

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Positive control:

not specified

Observations and examinations performed and frequency:

not specified

Sacrifice and pathology:

not specified

Other examinations:

not specified

Statistics:

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

Details on results:

not specified

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant changes were noted at the mentioned dose level

Critical effects observed:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

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") and("e" and(not "f")) ) and("g" and(not "h")) ) and("i" and(not "j")) ) and("k" and "l") )

Domain logical expression index: "a"

Referential boundary:The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Amine AND Anion AND Aromatic compound AND Cation AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "c"

Referential boundary:The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Aryl by Organic Functional groups

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Alkene AND Ammonium salt AND Aromatic amine AND Overlapping groups by Organic Functional groups (nested)

Domain logical expression index: "e"

Referential boundary:The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups OR SN2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as No alert found by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as Schiff base formation OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  OR SN2 OR SN2 >> Nucleophilic substitution on heteroarene sulfenamides OR SN2 >> Nucleophilic substitution on heteroarene sulfenamides >> Heteroarene sulfenamides  by Protein binding alerts for skin sensitization by OASIS v1.4

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as Alkaline Earth by Groups of elements

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.34

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.1

Conclusions:

The predicted No Observed Adverse Effect Level (NOAEL) for p,p',p''-tris(diethylamino)trityl alcohol is 1000 mg/kg bw/day.

Executive summary:

Repeated dose oral toxicity was predicted for p,p',p''-tris(diethylamino)trityl alcohol using SSS QSAR prediction database (2016). The study assumed the use of male and female Wistar rats in the combined repeated dose and reproduction / developmental screening study. The predicted No Observed Adverse Effect Level (NOAEL) for p,p',p''-tris(diethylamino)trityl alcohol is 1000 mg/kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is from K2 prediction database

Repeated dose toxicity: inhalation - systemic effects

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

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

Data from target chemical and read across chemical have been reviewed and summarized to determine the toxic nature of 4-(Diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)benzenemethanol:

Repeated dose oral toxicity was predicted for p,p',p''-tris(diethylamino)trityl alcohol (CAS no 596 -49 -6) using SSS QSAR prediction database (2016). The study assumed the use of male and female Wistar rats in the combined repeated dose and reproduction / developmental screening study. The predicted No Observed Adverse Effect Level (NOAEL) for p,p',p''-tris(diethylamino)trityl alcohol is 1000 mg/kg bw/day.

In a study on read across performed by Borzelleca et al (1990), Combined Repeated dose carcinogenicity study was performed to evaluate the toxic nature of Brilliant Blue FCF (RA CAS no 3844 -45-9). FD & C Blue No. 1 was fed to CD-1 mice as a dietary admixture in lifetime toxicity/carcinogenicity studies at dose levels of 0.0%, 0.0%, 0.5%, 1.5% or 5.0% (0, 0, 714.28, 2142.85 or 7142.85 mg/Kg bw/day) in a lifetime toxicity/ carcinogenicity study. The maximum exposure time was 104 wk for both males and females. Dietary concentration of 5.0% (7354 mg/kg/day and 8966 mg/kg/day for male and female mice, respectively) FD & C Blue No. 1 to mouse for 104 weeks did not demonstrate consistent biologically significant, compound-related adverse effects on behavior, morbidity, mortality, haematology, general physical observations. Thus, the no-observed-adverse-effect level (NOAEL) established in this study is a dietary concentration of 5.0% (7354 mg/kg/day and 8966 mg/kg/day for male and female mice, respectively).

In a subchronic repeated dose toxicity study, SPF Carworth Farm E male and female rats were treated with Blue VRS at a concentration of 0.0, 0.3, 0.75, 1.5 and 3.0 % (0, 150, 375, 750 and 1500 mg/kg/day) orally. Impairment of growth, Reduction in food consumption, compound intake and bluish-green and slightly more acid urine were observed in 750 and 1500 mg/Kg/day (1.5 and 3.0 %) treated male and female as compared to control. In addition, Fatty changes in the liver of female rat and increase number of active acini in the thyroids of male rat of 750 and 1500 mg/Kg/day (1.5 and 3.0 %) treated animals. Blue material in the lumen of convoluted tubules associated with a coloured line observed at the cortcomedullary junction of kidney in male of 1500 mg/Kg/day (3.0 %) treated dose groups but this was not necessarily attributable to Blue VRS. Histological changes associated with acinal activity occur in response to stress of various kinds were noted. Therefore, the no observed adverse effect level (NOAEL) was considered to be 375 mg/kg/day (0.75 %) when SPF Carworth Farm E male and female rats were treated with Blue VRS orally for 90 days.

Based on the data summarized, 4-(Diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)benzenemethanol is not likely to be toxic upon repeated oral exposure by oral route.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

Data is from prediction database;  The predicted No Observed Adverse Effect Level (NOAEL) for p,p',p''-tris(diethylamino)trityl alcohol is 1000 mg/kg bw/day.

Justification for classification or non-classification

Based on the data summarized, 4-(Diethylamino)-alpha,alpha-bis(4-(diethylamino)phenyl)benzenemethanol is not likely to be toxic upon repeated oral exposure by oral route.