TCA

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
Basic toxicokinetics: Key studies: The plasma concentrations of sodium trichloroacetate in rats versus those in mice were quite comparable following an oral dose of 20 or 100 mg/kg sodium trichloroacetate. The initial plasma levels of sodium trichloroacetate observed with a dose of 100 mg/kg were approximately 40% higher in rats relative to those of mice. This difference was no longer apparent 3 hr after dosing with sodium trichloroacetate and the elimination curves were essentialIy the same. The higher initial blood concentrations of sodium trichloroacetate in rats resulted in a signiftcantly greater AUC value. The Cmax for sodium trichloroacetate in rat and mice given the lower dose were the same, aIthough the AUC values were somewhat greater in rats compared to those in mice. Estimates of the kinetic parameters of sodium trichloroacetate in plasma were very similar in rats and mice at both dose levels administered, although the t1/2 was somewhat longer in rats than in mice at the lower dose, resulting in lower clearance values in rats.
The plasma concentrations and AUC of GOG were comparable in rats and mice following administration of sodium trichloroaceate. The Cmax for GOG was proportional to dose in rats and somewhat less than proportional with increasing dose in mice. In both species, the KE for GOG was between 0.2 and 0.5 hr(-1).

Additional information

Basic toxicokinetics:

Key studies: The plasma concentrations of sodium trichloroacetate in rats versus those in mice were quite comparable following an oral dose of 20 or 100 mg/kg sodium trichloroacetate. The initial plasma levels of sodium trichloroacetate observed with a dose of 100 mg/kg were approximately 40% higher in rats relative to those of mice. This difference was no longer apparent 3 hr after dosing with sodium trichloroacetate and the elimination curves were essentialIy the same. The higher initial blood concentrations of sodium trichloroacetate in rats resulted in a signiftcantly greater AUC value. The Cmax for sodium trichloroacetate in rat and mice given the lower dose were the same, aIthough the AUC values were somewhat greater in rats compared to those in mice. Estimates of the kinetic parameters of sodium trichloroacetate in plasma were very similar in rats and mice at both dose levels administered, although the t1/2 was somewhat longer in rats than in mice at the lower dose, resulting in lower clearance values in rats. The plasma concentrations of sodium dichloroacetate that result from metabolism of sodium trichloroacetate were dissimilar. Concentrations of sodium dichloroacetate in the plasma of mice were slightly higher than those in rats when the 20 mg/kg dose of sodium trichloroacetate was given, but at 100 mg/kg the Cmax for sodium dichloroaceate in rats was 30 nmol/mL compared to 5 nmol/mL in mice given the same dose. The AUC values for sodium dichloroaceate in rats were also disproportionately increased, rising 100-fold from 1 to 12 nmol/mL/hr in rats given 20 and 100 mg/kg sodium trichloroacetate, respectively. Mice did not display the marked increase in Cmax and the increases in AUC values were only exaggerated 2-fold over those expected with the 5-fold increase in dose. The plasma concentrations and AUC of GOG were comparable in rats and mice following administration of sodium trichloroacetate. The Cmax for GOG was proportional to dose in rats and somewhat less than proportional with increasing dose in mice. In both species, the KE for GOG was between 0.2 and 0.5 hr(-1).

Discussion on bioaccumulation potential result:

Key studies: In vivo: In rats: Following an oral dose of 20 mg/kg, the Cmax was 230 ± 10 nmol/mL; the AUC was 2530 ± 70 nmol/mL/h; the half-life was 7.0 h; the volume of distribution: 365 mL/kg; and the Clearance: 36 mL/kg.h. After an oral dose of 100 mg/kg, the Cmax was 1200 ± 100 nmol/mL; the AUC was 10000 ± 600 nmol/mL/h; the half-life was 5.8 h; the volume of distribution: 485 mL/kg; and the Clearance: 58 mL/kg.h.

In mice: Following an oral dose of 20 mg/kg, the Cmax was 230 ± 10 nmol/mL; the AUC was 2020 ± 60 nmol/mL/h; the half-life was 4.2 h; the volume of distribution: 335 mL/kg; and the Clearance: 55 mL/kg.h. After an oral dose of 100 mg/kg, the Cmax was 790 ± 60 nmol/mL; the AUC was 7180 ± 210 nmol/mL/h; the half-life was 5.8 h; the volume of distribution: 555 mL/kg; and the Clearance: 66 mL/kg.h.