Kinetics of monochloroacetic acid at subtoxic and toxic doses in rats after single oral and dermal administrations.

Rats were administered a single oral (10 [subtoxic] or 225 [toxic, LD20] mg/kg) or dermal (125 mg/kg, LD20) dose of 14C-monochloroacetic acid (MCA) and the time-course (0.25, 0.75, 2, 4, 8, 16, and 32 h postadministration) of radioactivity determined in plasma, tissues, and excreta. At the subtoxic oral dose, concentration of 14C-MCA peaked at 0.1% of dose by 2 h. Most tissue profiles of MCA paralleled that of plasma with few exceptions. At the toxic oral dose, tissue concentrations remained initially below those seen after the subtoxic dose, because stomach retained most of the toxic dose for up to 8 h. Peak plasma concentration was reached within 0.25 h without an apparent subsequent uptake phase. Most of the dermal dose rapidly penetrated into the skin (>95% within 0.25 h) and remained sequestered there and released slowly. Concentration in plasma peaked at 0.36% of dose by 0.75 h and remained constant for up to 4 h. Peak tissue concentrations were reached between 2 and 4 h. Within 0.75 h, 9% of the dermally absorbed dose was metabolized by liver and eliminated through bile, all of which was subsequently reabsorbed. Two percent of MCA appeared in colon by 0.75 h, apparently as a result of direct transport through GI-wall in retrograde movement. About 70-80% of radioactivity recovered from the small intestine of orally dosed rats was parent compound. Fecal elimination was negligible ( 400 and < 450) and 175 (LD50 145) mg/kg after oral and dermal exposure, respectively.