Registration Dossier
Registration Dossier
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EC number: 206-839-0 | CAS number: 381-73-7
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
Data source
Reference
- Reference Type:
- publication
- Title:
- Tissue distribution, excretion, and urinary metabolites of dichloroacetic acid in the male Fischer 344 rat
- Author:
- Lin EL, Mattox JK, Daniel FB.
- Year:
- 1 993
- Bibliographic source:
- J Toxicol Environ Health. 1993 Jan;38(1):19-32
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other:
- Principles of method if other than guideline:
- The disposition of dichloroacetic acid (DCA) was investigated in Fischer 344 rats over the 48 hr after oral gavage of 282 mg/kg of 1- or 2-(14C)-DCA (1-DCA or 2-DCA) and 28.2 mg/kg of 2-DCA
- GLP compliance:
- no
Test material
- Reference substance name:
- Dichloroacetic acid
- EC Number:
- 201-207-0
- EC Name:
- Dichloroacetic acid
- Cas Number:
- 79-43-6
- IUPAC Name:
- dichloroacetic acid
- Reference substance name:
- dichloroacetic acid (DCA)
- IUPAC Name:
- dichloroacetic acid (DCA)
- Test material form:
- other: Liquid
- Details on test material:
- - Name of test material (as cited in study report): (14C)-DCA
- Molecular formula (if other than submission substance): C2H2Cl2O2
- Molecular weight (if other than submission substance): 128.94 g/mol
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): NA
Constituent 1
Constituent 2
- Radiolabelling:
- yes
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- not specified
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on exposure:
- The disposition of dichloroacetic acid (DCA) was investigated in Fischer 344 rats over the 48 hr after oral gavage of 282 mg/kg of 1- or 2-(14C)-DCA (1-DCA or 2-DCA) and 28.2 mg/kg of 2-DCA.
- Duration and frequency of treatment / exposure:
- 48 hours
Doses / concentrations
- Remarks:
- Doses / Concentrations:
282 mg/kg of 1- or 2-(14C)-DCA (1-DCA or 2-DCA) and 28.2 mg/kg of 2-DCA
- No. of animals per sex per dose / concentration:
- Details not available
- Control animals:
- not specified
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- DCA was absorbed quickly
- Type:
- distribution
- Results:
- The major route of disposition was through exhalation of carbon dioxide and elimination in the urine.
- Type:
- metabolism
- Results:
- The primary metabolic pathway for dichloroacetic acid (DCA) involves oxidative dechlorination to form glyoxylate.
- Type:
- excretion
- Results:
- Excretion of dichloroacetic acid was through exhalation of carbon dioxide and elimination in the urine
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Absorption: DCA was absorbed quickly
- Details on distribution in tissues:
- Distribution: The major route of disposition was through exhalation of carbon dioxide and elimination in the urine. After 48 hr, 36.4%, 26.2%, and 20.8% of the dose was retained in the tissues of rats administered 28.2 and 282 mg/kg of 2-DCA and 282 mg/kg of 1-DCA, respectively.
- Details on excretion:
- Excretion: Excretion of dichloroacetic acid was through exhalation of carbon dioxide and elimination in the urine.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- glycolic acid
glyoxylic acid and
oxalic acid
The metabolic pathway is presented as a figure below (Source: Toxicological review of Dichloroacetic acid, in support of Summary Information in the Integrated Risk Information System (IRIS), August 2003, USEPA)
Any other information on results incl. tables
Metabolism: The primary metabolic pathway for dichloroacetic acid (DCA) involves oxidative dechlorination to form glyoxylate. The major urinary metabolites were glycolic acid, glyoxylic acid, and oxalic acid. DCA and its metabolites accumulated in the tissues and were eliminated slowly.
Organs exhibiting radioactivity: Liver
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): high bioaccumulation potential based on study results
Disposition is often used to describe the time-course of movement of chemicals through the body. In the present study, after 48 hr, 36.4%, 26.2%, and 20.8% of the dose was retained in the tissues of rats administered 28.2 and 282 mg/kg of 2-DCA and 282 mg/kg of 1-DCA, respectively. Also, DCA and its metabolites accumulated in the tissues and were eliminated slowly. This suggest high bio-accumulation potential of dichloroacetic acid (DCA) based on study results - Executive summary:
Disposition is often used to describe the time-course of movement of chemicals through the body. In the present study, after 48 hr, 36.4%, 26.2%, and 20.8% of the dose was retained in the tissues of rats administered 28.2 and 282 mg/kg of 2-DCA and 282 mg/kg of 1-DCA, respectively. Also, DCA and its metabolites accumulated in the tissues and were eliminated slowly. This suggest high bio-accumulation potential of dichloroacetic acid (DCA) based on study results
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