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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The data are generated according to an internationally accepted guideline. All study parameters are well documented and are based on the specific guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
according to
Guideline:
EPA OPPTS 870.7485 (Metabolism and Pharmacokinetics)
Deviations:
no
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
14C-Triazole with specific activities of 67.1 µCi/mg (low dose), 0.67 µCi/mg (mid-dose) and 0.034 µCi/mg (high-dose) were used in this study. The radioactive purity was > 98 % by TLC analysis.
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
acetone
Details on exposure:
A stock solution of 14C-Triazole in 10 ml acetone was prepared for each level. One milliliter of acetone from each stock solution was brought to volume (10ml) with deionized water. A dose of 1 ml was administered to each rat with an intubation needle connected to a 3 ml syringe.
Duration and frequency of treatment / exposure:
single oral dose
Doses / concentrations
Remarks:
Doses / Concentrations:
0.08, 9.8 and 173.1 mg/rat
No. of animals per sex per dose:
three groups of rats (each consisting of 2 males and two females)
Control animals:
no
Details on study design:
Daily samples of urine and feces were collected from the rats. Seven days (168-hours) after dosing, the rats were sacrificed and samples were taken (blood, heart, lungs, spleen. Kidney, liver, brain, muscle, fat and gonads). Blood was separated into plasma and red blood sells by centrifugation, using heparin as the anticoagulant.
Heights of tissues other than muscle, fat, plasma, and red blood cells were obtained by direct weighing. These tissue weights (muscle, fat, plasma and red blood cells) were calculated from the weight of the rat at dosing using percentages of the body weight.
Radioassay procedures: Urine samples were aliquoted directly. Feces and tissues were homogenized.
All counting was carried out in a Beta Tracor Model 6895 liquid scintillation counter.

Radioactivity Measurements: radioassays were done by external standarisation using a Beta Tracor Model 6895 counter.

Results and discussion

Main ADME results
Type:
excretion
Results:
The main route of excretion for all dose levels was the urine averaging 89.3.

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
At sacrifice, tissue levels were very low for all dose levels. These values were at or below the limit of quantification for each dose level.
Details on excretion:
The main route of excretion was urine and recoveries averaged 92.0 , 86.2 and 89.8 % for the low. mid and high dosed animals, respectively. Recovery of the radioactivity in feces averaged 8.1, 15.2 and 7.9 % for the low, mid and high dosed animals.
No significant differences were observed in excretion patterns between different sexes of rats of the same dose level.
Excretion of the radioactivity during the first 48 hours after administration accounted for 97.7 for low, 97.6 % for mid and 84.8 % for high dose animals.
The average total recoveries of administered 14C-Triazole was excellent for low (101.0 %), mid (102.8 %) and high (100.2 %) dosed animals.

Metabolite characterisation studies

Metabolites identified:
not measured

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
Conclusion from study report:
Based upon the rapid absorption and elimination of the dose with concurrent low tissue retention, it was concluded that there would be only a minimal risk of adverse effects to mammals administered triazole at levels up to 9,000 ppm in their diet.