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Toxicological information

Basic toxicokinetics

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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

Referenceopen allclose all

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 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

Reference
Name:
Unnamed
Type:
Constituent

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.