Case ReportPostmortem distribution of acephate and its metabolite methamidophos in body fluids and organ tissues of an intoxication case
Introduction
Acephate (Fig. 1) has been used as an organophosphate insecticide since 1973 in Japan [1], and since 1974 in the USA [2], and a number of types (particle type, 50% aqueous solution type) are produced by Sumitomo Chemical (Osaka, Japan) and other companies. Acephate is stable at acidic and neutral pH, but is slightly unstable at an alkali pH (e.g. pH 8.2) [1]. Acephate and its metabolite, methamidophos, are both (acetyl)cholinesterase inhibitors [3]. The activity of acephate is weaker than that of methamidophos because PO of methamidophos interacts with the Ser 200 of acetylcholinesterase (AChE), whereas PO and CO of acephate may both interact with the enzyme [4]. Acephate at a concentration less than 1.25 mM (approximately 230 ppm) in human serum did not inhibit the activity of cholinesterase (ChE) [5]. These findings suggest that the serum ChE activity of humans exposed to acephate is not affected when serum acephate concentrations are less than 200 ppm [5]. H2O2 levels in renal tubular epithelial cells (LLC-PK1) exposed in vitro to an acephate concentration of 2500 ppm for 72 h were significantly elevated and the formation of malondialdehyde (MDA) was also enhanced, which demonstrated the toxic effects of acephate on renal tubular cells [6]. When pregnant ICR (CD-1) mice were administered sublethal doses of 0 (distilled water), 7, 14, and 28 mg/kg/day acephate by gavage on gestational days 6–15, acephate induced maternal and developmental toxicity at 28 mg/kg/day [7]. In rats injected intraperitoneally with acephate (500 mg/kg) or methamidophos (5 mg/kg), tissue methamidophos concentrations were significantly higher in acephate-treated rats than in methamidophos-treated rats, and the inhibition of AChE activity was not consistent with the amount of methamidophos that formed metabolically. These findings support the hypothesis that acephate may deduce the toxicity of methamidophos, and that the protective action of acephate plays a role in overall toxicity [7]. In the same study, the effects of methamidophos on the adrenal cortex were suggested to be mediated by the pituitary gland, while those of acephate may have been due to a direct acephate-gland interaction [8]. The oral lethal dose (LD) 50 of acephate is 361 mg/kg in mice [3] and 945 mg/kg in rats [3]. Some human data have been reported for toxic and lethal cases [[9], [10], [11]].
We herein presented an acute intoxication case involving Ortoran®. Acephate and its active metabolite methamidophos were measured using GC–MS in the body fluids and organ tissues obtained. To the best of our knowledge, we are the first to report the concentrations of acephate and methamidophos in organ tissues.
Section snippets
Case history and autopsy findings
A man in his 60 s was found dead in his car with a 100-mL bottle containing approximately 50 mL of the organophosphate pesticide, Ortoran®. The man was relatively small (149 cm) and weighed 44 kg. There were no injuries on his body. The diameters of the left and right pupils were both 5 mm. An internal examination showed no injuries, diseases, or congenital malformations. The brain weighed 1410 g and had a normal shape and morphology. The heart weighed 370 g and had a normal shape; however, the
Results and discussion
Screening by GC–MS of the stomach contents identified acephate and methamidophos. Methamidophos, acephate-d6 (IS), acephate, and dimethoate (IS) extracted from heart blood were separated using the DB-1MS column at retention times of 3.60, 4.71, 4.74, and 6.04 min, respectively (Fig. 2). Extraction effects by pH changes for acephate and methamidophos were shown in Fig. 3. These results demonstrated that the highest peak area of acephate was pH 6, while that of methamidophos was pH 7. Therefore,
Conclusion
We herein presented a man in his 60 s who orally ingested a pesticide containing acephate. The postmortem distribution of acephate and its active metabolite, methamidophos, in the body fluids and organ tissues was assessed as shown in Table 4. Based on toxicological data together with autopsy findings, the cause of death was suggested to be acute fatal poisoning by the pesticide containing acephate and its active metabolite, methamidophos. Concentration ratios between acephate and methamidophos
Acknowledgment
We thank Mr. Akira Minabe for his assistance.
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