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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: Comparable to guideline study with acceptable restrictions: only one dose level was used; no detailed data provided (only charts)

Data source

Reference
Reference Type:
publication
Title:
Oral and dermal application of 2,4-dichlorophenoxyacetic acid sodium and dimethylamine salts to male rats: investigations on absorption and excretion as well as induction of hepatic mixed-function oxidase activities
Author:
Knopp, D. and Schiller, F.
Year:
1992
Bibliographic source:
Arch Toxicol, 1992, 66, 170-174

Materials and methods

Objective of study:
absorption
excretion
Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
only one dose level was used; no detailed data provided (only charts)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Spritz-Hormit; 2,4-D sodium salt
- Analytical purity: soluble powder
- Analytical purity: 82%
- Source of the substance: "Chemisches Kombinat”, Bitterfeld, GDR
- Specific activity (if radiolabelling): not stated
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
other: F1-hybrid of the inbred strains WELS/FOHM and BD IX/Halle
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 320 ± 30 g
- Individual metabolism cages: yes (made of glass, Altromin)
- Diet: Kaninchen-Versuchsfutter ad libitum (Getreidewirtschaft Bernau, Germany)
- Water: tap water ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
5 g of Spritz-Hormit in 1 L water

VEHICLE
- Concentration in vehicle: 4.10 mg/mL
- Amount of vehicle (if gavage): 200 µl


Duration and frequency of treatment / exposure:
single administration
Doses / concentrations
Remarks:
Doses / Concentrations:
2.6 mg/kg body weight
No. of animals per sex per dose / concentration:
5
Control animals:
yes, concurrent vehicle
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Urine samples were collected in glass vessels at the urine funnel spout of each metabolism cage.
- Time and frequency of sampling: Urine was collected twice daily at specified times over a 69 h period. The concentration of 2,4-D was determined immediately.
- other: At the end of the study each animal was sacrificed and blood was taken from the abdominal aorta into heparinized tubes. Blood plasma was obtained by centrifugation. 2,4-D determination was performed by radioimmunoassay (Knopp et al. 1985). If necessary, urine and plasma were diluted with water in order to reach the optimal measuring range of the radioimmunological method. Standard stock solutions of 2,4-D were prepared in methanol. Appropriate dilutions were added to urine or plasma of untreated control rats. Recovery of 2,4-D from fortified samples was 95 - 104%. All samples were assayed in triplicate in a scintillation counter and the data calculated as outlined by Rodbard using a radioimmunoassay program.

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Cumulative 2,4-D urinary excretion reached about 92% of the applied dose. Assuming an additional 3-4% fecal elimination, systemic availability of the oral dose was nearly 100%.
Type:
excretion
Results:
One day after dosing approx. 90% of DMA was excreted via urine. Three days after exposure, urinary 2,4-D could no longer be detected in 50% of the animals.

Toxicokinetic / pharmacokinetic studies

Details on excretion:
Peak concentrations appeared in the 20.5 hours urine spot samples and were followed by a gradual decline over the next 10 hours.
In some animals the 2,4-D concentration reached the "zero"-level (concentrations below the detection limit of 1 µg/L of the analytical method)
nearly three days after oral administration.
Toxicokinetic parameters
Test no.:
#1
Toxicokinetic parameters:
Tmax: 20.5

Metabolite characterisation studies

Metabolites identified:
no

Any other information on results incl. tables

In all animals, 2,4 -D plasma concentrations were not detectable at the end of the experiment or at least lower than 10 ppb. The volume of urine of the treated animals was significantly increased when compared with the controls.

Applicant's summary and conclusion

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