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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with minor deviations. (Distribution was not investigated.)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1991

Materials and methods

Objective of study:
metabolism
Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 85-1 (Metabolism and Pharmacokinetics)
Qualifier:
equivalent or similar to
Guideline:
EU Method B.36 (Toxicokinetics)
Deviations:
yes
Remarks:
Distribution was not investigated.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ziram
- Lot no.:
14C-Ziram: 027F9221
Nonradiolabeled Ziram: Technical
- Purity:
14C-Ziram: 96.9%
Nonradiolabeled Ziram: 99%

Radiolabelling:
yes
Remarks:
14C-Ziram

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River, US
- Age at study initiation: 44 days (m); 51 days (f)
- Weight at study initiation: 149-169 g (m); 145-162 g (f)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Duration and frequency of treatment / exposure:
Single and multiple (15 days daily) application
Doses / concentrations
Remarks:
Doses / Concentrations:
Single: 15 and 352 mg/kg
Multiple: 15 mg/kg (14x nonradiolabeled; 1x radiolabeled)
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on dosing and sampling:
- Tissues and body fluids sampled: air, urine, faeces, blood, several organs

The CO2 trapping solution and the volatile traps were collected at 0-4, 4-8, 8-12, and 12-24 h following administration of the radiolabeled Ziram and daily thereafter for a total of 4 days. Urine and faeces samples were collected at 0-6, 6-12, and 12-24 hours after the radiolabeled dose and daily thereafter for a total of 7 days. Urine and faeces were collected in plastic containers surrounded by ice. At the end of the collection period, the animals were anesthetized with halothane and exsanguinated by cardiac puncture. Blood (2 to 5 mL) was collected and weighed in heparinized tubes and saved for radioanalysis. After sacrifice the cages were washed with a 1.0% trisodium phosphate solution which was saved for analysis.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The mean 14C recovery ranged from 79% to 92% of the total doses administered.


Details on distribution in tissues:
The mean total radioactivity retained in the tissues and carcasses ranged from 1.11% to 1.92% of the total dose administered. For the low dose groups, the residue levels in the blood and tissues ranged from 0.05 to 2.5 ppm (µg 14C-Ziram equivalents/g sample). The highest levels were found in blood, liver, kidney, heart, lungs, spleen and thyroid gland.
Details on excretion:
The majority of the radioactivity was found in urine (17% to 35%), faeces (9% to 18%), and expired air (36% to 53%). The rate of elimination was relatively fast; the majority of the radioactivity was eliminated within 48 hours after dosing.
No apparent sex-related differences were observed for 14C elimination or distribution for any of the treated groups.

Metabolite characterisation studies

Metabolites identified:
yes

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results