Sodium chloroacetate

Specific investigations: other studies

Administrative data

Endpoint:

biochemical or cellular interactions

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:

other: Mechanistic study; no study according to guidelines

Data source

Reference

Reference Type:

publication

Title:

Inhibition of pyruvate carboxylase by chloropyruvic acid and related compounds

Author:

Doedens D, Ashmore J

Year:

1972

Bibliographic source:

Biochem. Pharmacol. 21(12), 1745-1751

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Effects on CO2 fixation in rat liver slices with lactate and pyruvate as substrate was measured. Mitochondrial CO2 fixation was investigated. Further, effects on incorporation of 14C from [U-14C]L-alanine into glucose and CO2 and on production of ketone bodies was investigated and the inhibition of CO2 fixation in acetone powder extracts.

GLP compliance:

not specified

Type of method:

in vitro

Test material

Test material information

Constituent 1

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:

Chloroacetic acid was supplied by Pfaltz and Bauer.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

Rats weighing 200-350 g were used. Animals in liver slice experiments were fasted overnight; others were fed ad lib. Rats were sacrificed by stunning and exsanguination.

Administration / exposure

Route of administration:

other: not applicable

Vehicle:

other: not applicable

Details on exposure:

Liver slices were incubated with chloroacetic acid.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

N.A.

Frequency of treatment:

N.A.

Post exposure period:

N.A.

Doses / concentrations

Remarks:

Basis: nominal conc. 0.1, 1-10 mM

No. of animals per sex per dose:

Not specified

Control animals:

no

Examinations

Examinations:

Effects on CO2 fixation in rat liver slices with lactate and pyruvate as substrate was measured. Mitochondrial CO2 fixation was investigated. Further, effects on incorporation of 14C from [U-14C]L-alanine into glucose and CO2 and on production of ketone bodies was investigated and the inhibition of CO2 fixation in acetone powder extracts.

Positive control:

No

Results and discussion

Details on results:

Incorporation of 14CO2 into glucose in slices incubated with lactate or pyruvate was inhibited by chloropyruvic acid. At 0·1 mM, chloropyruvic acid (CPA) and related compounds, including chloroacetic acid, inhibited incorporation into glucose of label from [U-14C]alanine without affecting production of ketone bodies or 14CO2. Inhibition was not observed in similar preparations using succinate as substrate. In mitochondria, concentrations of 1-10 mM CPA inhibited CO2 fixation by 56-95 per cent. In acetone powder extracts, CPA at 1-10 mM reduced CO2 fixation by 21-86 per cent. Interconversion between CPA and chlorolactate was not catalyzed by lactic dehydrogenase, nor did these compounds inhibit this enzyme.

Applicant's summary and conclusion

Conclusions:

The data from this mechanistic study in rat liver indicate that CPA and related acids (e.g. monochlororacetic acid) may inhibit gluconeogenesis by specific inhibition of pyruvate carboxylase. Whether or not this metabolic effect is involved in the development of sterility after administration of CPD remains to be determined.