Dimethylammonium 2,4-dichlorophenoxyacetate

Basic toxicokinetics

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 raw 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 raw data provided (only charts)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dimethylammonium 2,4-dichlorophenoxyacetate

EC Number:

217-915-8

EC Name:

Dimethylammonium 2,4-dichlorophenoxyacetate

Cas Number:

2008-39-1

Molecular formula:

C8H6Cl2O3.C2H7N

IUPAC Name:

dimethylammonium 2,4-dichlorophenoxyacetate

Details on test material:

- Name of test material (as cited in study report): Spritz-Hormin 600; 2,4-D dimethylamine salt (DMA)
- Physical state: aqueous concentrate
- Analytical purity: 50%
- 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:
6 mL of Spritz-Hormin 600 (analytical purity 50%) in 1 L water

VEHICLE
- Concentration in vehicle: 3.00 mg/mL
- Amount of vehicle (if gavage): 200 µl

Duration and frequency of treatment / exposure:

single administration

Doses / concentrations

Remarks:

Doses / Concentrations:
1.9 mg/kg body weight

No. of animals per sex per dose / concentration:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Dose is representative of occupational exposure

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 tim pointss 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 results

Main ADME results 1

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%.

Main ADME results 2

Type:

excretion

Results:

One day after dosing approx. 90% of DMA was excreted via urine. Three days after exposure, urinary 2,4-D content could no longer be detected in 50% of the animals.

Toxicokinetic / pharmacokinetic studies

Details on excretion:

The highest concentrations of DMA were always measured in the 4.5 h-samples. Peak concentrations were followed by a gradual decline over the next 10 hours. In some animals the concentration reached the "Zero"-level (concentration below the detection limit of 1 µg/L of the analytical method) approx. three days after administration.

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

Tmax: 4.5 h

Toxicokinetic parameters 2

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: >20.5 h

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

After oral application the volume of urine was significantly increased when compared with the control animals (p< 0.01).

Applicant's summary and conclusion

Conclusions:

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