4-(tert-butyl)-N-sec-butyl-2,6-dinitroaniline

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

Japanese Ministry of Agriculture, Foresty and Fisheries (MAFF) Guidelines

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EPA FIFRA GPLS, 40 CRF Part 160

Principles of method if other than guideline:

The pharmacokinetics was investigated in Sprague-Dawley CD rats (5 rats/sex/dose group) at two dose levels, 8 mg/kg body weight (low) and 800 mg/kg bw (high). Animals were administered a single dose of [14C]butralin by oral gaage. Prior to treatment, animals were cannulated wia the jugular vein and the cannula used to collect periodic blood samples.

GLP compliance:

yes (incl. QA statement)

Test material

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

8 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

800 mg/kg bw/day (nominal)

No. of animals per sex per dose / concentration:

5

Applicant's summary and conclusion

Conclusions:

Following a single oral administration of [14C]-butralin to Sprague Dawley rats at the dose-levels of 8.0 or 800 mg/kg bw, absorption and elimination rates of blood radioactive residues were moderately rapid.
At the low dose-level, females required a longer time to reach Cmax (8 hrs) than males (4 hrs), but the Cmax residue concentrations were similar in both sexes (1.05 and 1.18 ppm respectively in males and females). Therefore, the exposure (AUC) was approximately 2.6 times higher in females than in males (23.7 and 63.5 ppm.hrs respectively in males and females).
At the high dose-level the Cmax was only 50 times higher at the high dose-level than at the low dose-lvel, the AUC were approximately 136 times and 72 times higher (respectively in males and females) at the high dose-level than at the low dose-level.
At the low dose-level the T1/2 was longer in females than in males, indicating a possible difference in the elimination rate of butralin between sexes.
Although the Cmax at the high dose (mean 49.0 ppm versus 1,1 ppm at the low dose) did not increase linearly with dose, the exposure of the animals (AUC, mean 3829 ppm.hrs at the high dose versus 44 ppm at the low dose) did.