Sodium chloroacetate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

publication

Title:

Toxicokinetics of monochloroacetic acid: a whole body autoradiography study

Author:

Bhat et al

Year:

1990

Bibliographic source:

Toxicol. 63, 35-43

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Whole body autoradiograhphy; Sprague Dawley rats (3/group) were given a single iv dose of 0.07 mg/kg BW 1-14C-MCAA, transferred to metabolism cages and euthanized by CO after 5 minutes, 1, 4, 12, 24 and 48 hours after dosing. Animals were embedded in carboxymethylcellulose molds and frozen in hexane colled with solid carbon dioxide (-75C) until sectioning. 20 and 60 µm thick sections were sliced, exposed for 6-10 weeks (at -20C) on films, developed and printed.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

monochloroacetic acid

IUPAC Name:

monochloroacetic acid

Constituent 2

Reference substance name:

Chloroacetic acid

EC Number:

201-178-4

EC Name:

Chloroacetic acid

Cas Number:

79-11-8

Molecular formula:

C2H3ClO2

IUPAC Name:

2-Chloro-ethanoic acid

Details on test material:

- Name of test material (as cited in study report): monochloroacetic acid (MCAA)
- Radiochemical purity (if radiolabelling): >98%
- Specific activity (if radiolabelling): 16.1 mCi/mmol
- Locations of the label (if radiolabelling):1-14C-MCAA

Radiolabelling:

yes

Remarks:

1-14C-MCAA

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Indianapolis, IN
- Age at study initiation:
- Weight at study initiation:70-75 g
- Fasting period before study:
- Housing:
- Individual metabolism cages: yes
- Diet ad libitum):
- Water ad libitum):
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):12 h light/dark cycle

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

intravenous

Vehicle:

other: 10% Na2CO3

Duration and frequency of treatment / exposure:

single iv dose

Doses / concentrations

Remarks:

Doses / Concentrations:
0.07 mg/kg (40 µCi) 1-14C-MCAA in 10% Na2CO3 via tail vein, volume injection 25 µL

No. of animals per sex per dose / concentration:

3

Control animals:

no

Details on study design:

- Dose selection rationale: tracer dose

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Whole body: 5 minutes, 1, 4, 12, 24, 48 hours after administration

Statistics:

not performed

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Rapid accumulation after 5 minutes in liver and excretory system. MCAA and/or metabolites were present in excretory organ walls, such as kidney cortex and stomach walls; in certain areas of brown fat such as in the upper dorsal areas of the neck. Liver distribution was not homogenous. In circulatory system the uptake was less prominent than its accumulation in the tissues as indicated by greater uptake in the myocardial muscle when compared to blood. High radioactivity levels were found in esophagus and tracheal tissues.
At 1 hour radioactivity was extensively excreted into the small intestinal lumen, kidney contents and urinary bladder. Accumulation was prominent in brain, thymus, salivary glands and tongue.
At 4 hours the radioactivity in the brain was high and almost equal to that of the liver. The cerebellum showed higher accumulation as compared to other areas of the brain. Accumulation was seen in the spleen, pancreas, intestinal walls.
At 12 hours following treatment persistent accumulation of radioactivity was observed in the central nervous system; brain and spinal cord showed high radioactivity levels. Accumulation of radioacitivity in the thymus and pancreas was higher than in any other tissue.
Distribution and accumulation was for 24 and 48h comparable with the 12-hours time point.

Details on distribution in tissues:

see absorption

Details on excretion:

Most of the radioactivity was removed after 4 hours from the circulating fluids.

Metabolite characterisation studies

Metabolites identified:

no

Applicant's summary and conclusion

Conclusions:

Brain uptake was slow and steady-penetration BBB, even at low doses, not dose dependent.
Delayed and high uptake in thymus and spleen indicated strong interaction between blood cells. Active uptake by pancreas - indicated uptake in protein synthesis as a precursor amino acid.
First accumulation in hydrophilic tissues, at later times into carboxymethylcysteine tissues.