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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-GLP study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992

Materials and methods

Objective of study:
distribution
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Distribution of monochloroacetic acid after a single oral dose in rats by gavage. Animals were sacrificed after 4,8,12,24 and 48 hours.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
monochloroacetic acit (99+%, gold label) from aldrich chemical co, milwaukee, WI
1-14C-labeled monochloroacetic acid >98% pure; specific activity 2.4 mCi/mmol) from sigma chemical co, st louis, MO
Radiolabelling:
yes
Remarks:
1-14C-Monochloroacetic acid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Individual metabolism cages: yes/no
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

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

IN-LIFE DATES: From: To:
TEST ANIMALS
- Source:Harlan
- Weight at study initiation: 175 g
- Individual metabolism cages: yes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
not specified
Duration and frequency of treatment / exposure:
Two groups: single oral dose
One group, daily oral dose for 3 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1 mmole/kg bodyweigt 1-14C-MCAA
1 mmole/kg bodyweigt 1-14C-MCAA
No. of animals per sex per dose:
3/per time point
Control animals:
no
Details on study design:
- Dose selection rationale:
Determine distribution of MCAA after a single oral dose. A higher dose was applied to determine dose dependency. Dosing for 3 consecutive days was to investigate bioaccumulation
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, blood, plasma, Kidney, Liver, Intestine, Lung, Spleen, Heart, Brain and Testes
- Time and frequency of sampling: 4, 8, 12, 24, 48 after dosing

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: urine, faeces, blood, plasma, Kidney, Liver, Intestine, Lung, Spleen, Heart, Brain and Testes
- Time and frequency of sampling:4, 8, 12, 24, 48 after dosing
- From how many animals: 3 per time point, not pooled
- Method type(s) for identification: Liquid scintillation counting
- Limits of detection and quantification: not specified
Statistics:
two tailed student's t-test

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Absorbance was fast. highest levels in intestine and kidney at 4 and 8 hours after dosing, followed by lower levels in liver, spleen, testes, lung, brain and heart in decreasing order.
Details on distribution in tissues:
See table 1 & 2
Comparable distribution patterns with the higher dose: significant increase of radiolabel present (1.4 to 3.8 higher) in different tissues, except for liver and spleen
Details on excretion:
Elimination phase appears to be faster for intestine and kidney compared to other tissues. urinary excretion of MCAA and/or metabolites was 90% fo the dose after 24 hours.

Metabolite characterisation studies

Metabolites identified:
yes

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other:
Dose dependent accumulation of MCAA.