4-nitroaniline

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference 1

Reference Type:

publication

Title:

No information

Author:

Clayton, G. D. and F. E. Clayton (eds.).

Year:

1982

Bibliographic source:

Pattys Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 2468]**PEER REVIEWED**

Reference 2

Reference Type:

other: Authoritative data base

Title:

GCID: 48

Author:

[Clayton, G. D. and F. E. Clayton (eds.).

Year:

2011

Bibliographic source:

ACToR (Aggregated Computational Toxicology Resource);Clayton, G. D. and F. E. Clayton (eds.). Pattys Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 2468]**PEER REVIEWED**

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Data is from ACToR database

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

4-nitroaniline

EC Number:

202-810-1

EC Name:

4-nitroaniline

Cas Number:

100-01-6

Molecular formula:

C6H6N2O2

IUPAC Name:

4-nitroaniline

Details on test material:

- Name of test material (as cited in study report): 4-nitroaniline
- Substance type: Organic
- Physical state: solid

Radiolabelling:

yes

Remarks:

The clearance of [14C]PNA-derived radioactivity from various tissues was rapid and followed a two-component decay curve.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Administration / exposure

Route of administration:

other: oral and/or intravenous (iv)

Vehicle:

not specified

Doses / concentrations

Remarks:

Doses / Concentrations:
2-100 mumol/kg

Control animals:

not specified

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

4-nitroaniline (PNA)was absorbed through the gastrointestinal tract

Main ADME results 2

Type:

distribution

Results:

4-nitroaniline (PNA) was rapidly distributed throughout the tissues by oral and /or intravenous route

Main ADME results 3

Type:

excretion

Results:

The metabolites of 14[C] PNA were excreted primarily in the urine and to a lesser extent in feces

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The gastrointestinal absorption of PNA was near complete and was not affected by dose in the range studied (2-100 mumol/kg).

Details on distribution in tissues:

By oral or iv administration, PNA was rapidly distributed throughout the tissues and showed no marked affinity for any particular tissue

Details on excretion:

[14C]PNA was rapidly cleared by metabolism to nine metabolites which were excreted primarily in the urine and to a lesser extent in feces. Most (56%) of the urinary radioactivity was in the form of sulfate conjugates of two metabolites of PNA; the excretion of unmetabolized PNA was minimal (less than 3%). Biliary excretion of [14C]PNA was significant, however, much of this PNA-derived radioactivity underwent enterohepatic circulation and was subsequently excreted in urine.

Toxicokinetic parameters

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 1 hr.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

[14C]PNA was rapidly cleared by metabolism to nine metabolites

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
The results of this study indicate that, if metabolism is a detoxification process, the rapid metabolism and excretion of 4-nitroaniline minimize the
likelihood of significant toxicity from repeated exposure to PNA beyond that predicted by data from acute or short-term exposures.

Executive summary:

The disposition of p-[14C]nitroaniline (PNA) was studied in male F-344 rats following oral and/or intravenous (iv) administration. The gastrointestinal absorption of PNA was near complete and was not affected by dose in the range studied (2-100 mumol/kg). Following either oral or iv administration, PNA was rapidly distributed throughout the tissues and showed no marked affinity for any particular tissue. The clearance of [14C]PNA-derived radioactivity from various tissues was rapid and followed a two-component decay curve. The whole body half-life of PNA was approximately 1 hr. Within 3 days clearance of PNA-derived radioactivity from the body was almost complete. [14C]PNA was rapidly cleared by metabolism to nine metabolites which were excreted primarily in the urine and to a lesser extent in feces. Most (56%) of the urinary radioactivity was in the form of sulfate conjugates of two metabolites of PNA; the excretion of unmetabolized PNA was minimal (less than 3%). Biliary excretion of [14C]PNA was significant, however, much of this PNA-derived radioactivity underwent enterohepatic circulation and was subsequently excreted in urine. The results of this study indicate that, if metabolism is a detoxification process, the rapid metabolism and excretion of this compound minimize the likelihood of significant toxicity from repeated exposure to PNA beyond that predicted by data from acute or short-term exposures.