2,4-dinitrophenol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data have been obtained from secondary source.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Toxicological Profile for dinitrophenol

Author:

M. Olivia Harris, M.A; James J. Corcoran, Ph.D. (peer rewied by Dr. martin Alexander; Dr.Leon Koller; Dr.Norman Trieff)

Year:

1995

Bibliographic source:

U.S Department of Health and human Services, Public Health Service Agency for Toxic Substances and Disease Registry

Reference 2

Reference Type:

other: original reference

Title:

Analysis and kinetics of 2,4-dinitrophenol in tissues by capillary gas chromatography-mass spectrometry

Author:

Robert TA, Hagardorn AN.

Year:

1983

Bibliographic source:

J Chromatogr 276:77-84.

Materials and methods

Principles of method if other than guideline:

The half-time for absorption of 2,4-DNP following gavage administration of a single dose to mice was determined by a highly specific capillary gas chromatography (GC)-mass spectrometry (MS). Also serum and tissue levels of parent compound were quantitated by a highly specific capillary GC-MS method at 1-24 hours postdosing. Fractional absorption was not determined. Further details of method have not been specified.

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dinitrophenol

EC Number:

200-087-7

EC Name:

2,4-dinitrophenol

Cas Number:

51-28-5

Molecular formula:

C6H4N2O5

IUPAC Name:

2,4-dinitrophenol

Test animals

Species:

mouse

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

oral: gavage

Duration and frequency of treatment / exposure:

Single dose

Doses / concentrations

Remarks:

Doses / Concentrations:
22.5 mg/kg

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The half-time for absorption of 2,4-DNP following gavage administration was 0.5 hours.
Maximum values for the plasma concentration of 2,4-DNP were seen at 0.5 and 1.0 hours after dosing, giving additional evidence of rapid absorption.

Details on distribution in tissues:

Pharmacokinetic analysis indicated that a two-compartment open model best characterized the disposition of 2,4-DNP in the serum, liver, and kidney of mice given a gavage dose.
At 1-24 hours postdosing, although concentrations of 2,4-DNP were much lower in liver and kidney than in serum, similar half-times for absorption (t1/2 = 0.50-0.62 hours) and for the fast (alpha) (t1/2 = 1.00-1.20 hours) phase of biphasic elimination in all 3 tissues were determined. However, terminal (beta) elimination phase from kidney was very slow (t1/2 = 76.2 hours) compared with the beta phase in liver (t1/2 = 8.7 hours) and in serum (t1/2 = 7.7 hours).

Details on excretion:

Half-times for the slow terminal elimination phases were 7.7 hours for serum, 8.7 hours for liver, and 76.2 hours for kidney.

Applicant's summary and conclusion

Conclusions:

Absorption: maximum values of of 2,4-DNP plasma concentration show evidence of a rapid absorption.
Distribution: concentrations of 2,4-DNP were much lower in liver and kidney than in serum.The similar half-times for absorption and biphasic elimination in all three tissues (except terminal elimination phase in kidney) indicated that rapid exchange of 2,4-DNP occurred among these sites. The authors suggested that the apparent persistence of 2,4-DNP in the kidney could be related to tissue binding of the compound.
Excretion: based on results, the authors suggested that the apparent persistence of 2,4-DNP in the kidney could be related to tissue binding of the compound. Half-times for the slow terminal elimination phases were 7.7 hours for serum, 8.7 hours for liver, and 76.2 hours for kidney.

Executive summary:

Data have been obtained from secondary source, that mentions Robert TA, Hagardorn AN. 1983. Analysis and kinetics of 2,4-dinitrophenol in tissues by capillary gas chromatography-mass spectrometry. J Chromatogr 276:77-84.

Absorption, distribution and excretion of 2,4 -dinitrophenol were studied in mice treated by gavage administration with a single dose of 22.5 mg/kg.

A highly specific capillary gas chromatography (GC)-mass spectrometry (MS) technique was used to measure serum concentrations of 2,4-DNP at 1, 3, 6, 12, and 24 hours after dosing. Further details of method have not been specified.

The data were best represented by a two-compartment open model, and the analysis was performed accordingly. Fractional absorption was not determined.

Absorption: the half-time for absorption of 2,4-DNP following gavage administration was 0.5 hours.

Maximum values for the plasma concentration of 2,4-DNP were seen at 0.5 and 1.0 hours after dosing, giving additional evidence of rapid absorption.

Distribution: serum and tissue levels of the parent compound were quantitated by a highly specific capillary GC-MS method at 1-24 hours postdosing. Concentrations of 2,4-DNP were much lower in liver and kidney than in serum. Similar half-times for absorption (t1/2 = 0.50-0.62 hours) and for the fast (alpha) (t1/2 = 1.00-1.20 hours) phase of biphasic elimination in all 3 tissues were determined.

However, terminal (beta) elimination phase from kidney was very slow (t1/2 = 76.2 hours) compared with the beta phase in liver (t1/2 = 8.7 hours) and in serum (t1/2 = 7.7 hours). The similar half-times for absorption and biphasic elimination in all three tissues (except terminal elimination phase in kidney) indicated that rapid exchange of 2,4-DNP occurred among these sites. The authors suggested that the apparent persistence of 2,4-DNP in the kidney could be related to tissue binding of the compound.

Excretion: pharmacokinetic analysis indicated that a two-compartment open model best characterized the disposition of 2,4-DNP in the serum, liver, and kidney of mice given a gavage dose. Serum and tissue levels of parent compound were quantitated by a highly specific capillary GC-MS method at 1-24 hours postdosing. Half-times for the slow terminal elimination phases were 7.7 hours for serum, 8.7 hours for liver, and 76.2 hours for kidney. The authors suggested that the apparent persistence of 2,4-DNP in the kidney could be related to tissue binding of the compound.