4-(4-nitrophenylazo)-2,6-di-sec-butyl-phenol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2014

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other: (Q)SAR report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-(4-nitrophenylazo)-2,6-di-sec-butyl-phenol

EC Number:

410-610-2

EC Name:

4-(4-nitrophenylazo)-2,6-di-sec-butyl-phenol

Cas Number:

111850-24-9

Molecular formula:

C20 H25 N3 O3

IUPAC Name:

2,6-bis(butan-2-yl)-4-[2-(4-nitrophenyl)diazen-1-yl]phenol

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
On the basis of low oral and inhalation bioavailability, low volume of distribution, and predicted metabolism and excretion, 4-(4-nitrophenylazo)-2,6-di-sec-butylphenol is not expected to bioaccumulate.

Executive summary:

Experimental data on absorption, distribution, metabolism and excretion (ADME) are not available for 4-(4-nitrophenylazo)-2,6-di-sec-butylphenol. To assess the ADME potential of 4-(4-nitrophenylazo)-2,6-di-sec-butylphenol in human, the QSAR programs. ADMET predictor, Gastro Plus (v8.5, Simulations Plus Inc, Lancaster, CA, USA), and EPI Suite (version 4.1., USEPA, USA), were used. Additionally, published literature on metabolism of some analogs (Azo dyes) of 4-(4-Nitrophenylazo)-2,6-di-sec-butylphenol were also used. The predicted fractional absorption (Fa%) values of oral and inhalation for 4-(4- nitrophenylazo)-2,6-di-sec-butylphenol in human by GastroPlus are 0.59% and 0.48%, respectively.

As 4-(4-Nitrophenylazo)-2,6-di-sec-butylphenol can be metabolized to 4-amino-2,6-di-sec-butylphenol and 4-nitroaniline in human intestine, these two metabolites were further evaluated for fraction absorption (Fa%) and bioavailability(F%) from both dermal and oral exposure routes via GastroPlus. The predicted oral Fa% for 4-amino-2,6-di-sec-butylphenol and 4-nitroaniline were 99.8% and 100%, respectively; The predicted dermal Fa% for 4-amino-2,6-di-sec-butylphenol and 4-nitroaniline were 99.7% and 97.1%, respectively; The predicted oral F% for 4-amino-2,6-di-sec-butylphenol and 4-nitroaniline were 97.9% and 97.4%, respectively; The predicted dermal F% for 4-amino-2,6-di-sec-butylphenol and 4-nitroaniline were 97.9% and 78.1%, respectively.

CYP based metabolism is predicted for 4-(4-nitrophenylazo)-2,6-di-secbutylphenol with the systemic bioavailability (F%) of both oral absorption and inhalation predicted to be 0.37% and 0.29% for 4-(4-nitrophenylazo)-2,6-di-sec-butylphenol, respectively. The dermal permeability coefficient (Kp), the dermally absorbed dose per event (DAevent), and Dermal Absorbed Dose (DAD) for 4-(4-nitrophenylazo)-2,6-di-secbutylphenol were predicted as 0.793 cm/hr, 4 .0x10-5 mg/cm²-event (duration 10.5 h, time to reach steady state 46.4 h), 4.23 μg/kg-day (70 kg adult, water contact), respectively. The predicted human plasma protein binding upon absorption for 4-(4-nitrophenylazo)-2,6- di-sec-butylphenol is 98.7%. The volume of tissue distribution in humans was estimated to be low (2.33 L/kg). Based on the metabolism information of related Azo dyes, 4-(4-nitrophenylazo)-2,6-di-secbutylphenol will be metabolized to the hydroxylated metabolites (by CYP enzymes) and the corresponding phenolic compound and nitroaliline (by Azo reduction). The formed metabolites (and parent compound) can also be further metabolized water soluble metabolites (such as glucuronides and sulfates), which will be mainly excreted into urine and feces. On the basis of low oral and inhalation bioavailability, low volume of distribution, and predicted metabolism and excretion, 4-(4-nitrophenylazo)-2,6-di-sec-butylphenol is not expected to bioaccumulate.