Findings reveal dose- and time-dependent toxicity of monochloroacetic acid in rats, suggesting implications for clinical monitoring.
The effects of monochloroacetic acid (MCA) on serum concentrations of AST, m-AST, ALT, glu- cose, BUN, creatinine, lactate and pyruvate were examined in fasted rats. Rats were subcutaneously injected with saline or 108 (LD50) or 135 (LD70), 162 (LD90) mg/kg MCA solution. Blood samples were analyzed 1, 1.5 and 2 hr after injection. Serum AST, m-AST and ALT activities were increased dose-dependently. The serum glucose concentration increased over the 1-2 hrs in the control group and the LD50 group. In the LD70 group, the serum glucose concentration decreased over 1-1.5 hrs and did not change again by 2 hr. In the LD90 group, the serum glucose concentration decreased time-dependently over the 1-2 hrs. The BUN and creatinine concentrations increased dose- and time-dependently over the 1-2 hrs. The serum lactate and pyruvate concentrations increased dose- dependently. The LD90 group showed the greatest decrease in serum glucose concentration and the greatest increase in serum lactate, pyruvate and m-AST levels by 2 hr. Thus, MCA injured hepatic cells dose-dependently. A large amount of MCA caused severe damage to liver mitochondria after a 1.5-hr lag time. It was deduced that sharp changes in m-AST, glucose, lactate and pyruvate levels are closely related to a sudden worsening of the clinical MCA toxicity condition. Monitoring of the MCA concentration in blood just after exposure and any change of m-AST activity with time could possibly be of prognostic value, particularly in flagging any sudden worsening clinical condition.
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Toshina et al. (2004) studied this question.
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