1988 Volume 26 Issue 4 Pages 215-223
Oral administration of O, O, S-Trimethyl phosphorothioate (TMP), a known impurity present in technical grade malathion and other organophosphorus insecticides, causes a striking weight loss associated with hypophagia and cachexia in rats. Although it is known that treatment with TMP produces lung injury, the actual mechanism of delayed toxicity remains unknown. To determine the effect of TMP treatment on amino acid metabolism, we have investigated the amino acid pattern in plasma and in urine after treatment with TMP, using an Automatic Amino acid Analyzer. The concentrations of 41 amino acids were determined simultaneously. Together with treated (N=6) and control animals (N=6), we also used a pair-fed (N=3) group. Animals were dosed with TMP at 20 mg/kg in corn oil (approximately one third of the LD50) and sacrificed 72 hr after the treatment. During this period, the animals were put into metabolic cages and their urine was collected every 24 hrs. The amount of ethanolamine excreted in the urine of the treated animals increased as a function of time after treatment. Between 48 and 72 hr, the amount excreted (4311 ± 1160 nmoles : M ± SD) was 3 to 4 times higher than that in either the controls (1008±889 nmoles) or the pair-fed animals (1437 ± 300 nmoles). In plasma, the concentrations of ethanolamine and phenylalanine were higher in the TMP treated animals than in either the control or pair-fed animals. In contrast, the concentrations of valine, methionine and asparagine in the treated animals were similar to those in the control animals but higher than in the pair-fed animals. Clinical chemistry data, serum GOT, GPT, and urinary N-acetyl-β-D-glucosaminidase, were within normal ranges. These find-ings strongly indicate that amino acid utilization is impaired in delayed toxicity.
