Case ReportPostmortem distribution of chlorpyrifos-methyl, fenitrothion, and their metabolites in body fluids and organ tissues of an intoxication case
Introduction
Organophosphate chlorpyrifos-methyl (CPFM) and fenitrothion (MEP) are insecticides that are used worldwide (Fig. 1) [1]. CPFM is sometimes used in Japan, while MEP is one of the most frequently used organophosphate agents in Japan. The composition of CPFM varies (5% particles, 25 or 40% petroleum emulsion, 2% powder, or 0.4 or 20% oily agent), as does that of MEP (3% particles; 15, 50, 70, or 80% petroleum emulsion; 2 or 3% powder; 0.7, 10 or 40% oily agent; 40% aqueous solution) [2].
The oral lethal dose 50 (LD50) values of CPFM are 2254 and 2032 mg/kg in male and female mice, respectively, and 2472 and 1824 mg/kg in male and female rats, respectively [2]. The oral LD50 values of MEP are 1030 and 1040 mg/kg in male and female mice, respectively, and 330 and 800 mg/kg in male and female rats, respectively [2].
CPFM is hydrolyzed by esterases to 3,5,6-trichloro-2-pyridinol (TCPY) (Fig. 1) and dimethylthiophosphate (DMTP), which is further oxidized to dimethylphosphate [1]. TCPY may also be derived from chlorpyrifos [1]. TCPY is further conjugated with glucuronic acid and excreted in urine. MEP is hydrolyzed to 3-methyl-4-nitrophenol (3MNP) (Fig. 1) and DMTP [1], [3]. 3MNP also conjugates with glucuronic acid, and all 3MNP (free and conjugated forms) is excreted at an average of 67–76% of the daily dose in urine [1]. The nitro group of MEP is also metabolized to the amine form (aminofenitrothion), which is further embolized to acetylaminofenitrothion [4]. In another pathway, MEP is oxidized to fenitrooxon [1], [3].
CPFM, MEP, organophosphates and their metabolites have been analyzed using gas chromatography (GC)–mass spectrometry (MS) [5], [6], [7], [8], [9] and liquid chromatography (LC)–MS systems [10], [11], [12]. TCPY has been examined by GC–MS [9] and by LC–MS [11] systems, and 3MNP has also been done by GC–MS [8], [9] and by LC–MS [12] systems.
A previous study found that the toxic blood level of MEP was 0.26 µg/g 4 h after its ingestion [5]. Serum MEP concentrations averaged 3.0 ± 1.9 µg/mL at admission in 10 adult cases that survived acute ingestion [13]. Serum MEP levels in another three surviving cases ranged between 6.4 and 17 µg/mL [14], [15], [16].
The postmortem distribution of CPFM has only been reported in a fatal case of a man who ingested CPFM and dichlorvos [17]. Previous studies have described fatal intoxication cases with MEP [1], [13], [15], [18].
CPFM and MEP and their metabolites, TCPY and 3MNP, respectively, were determined using GC–MS. We herein presented an acute intoxication case with CPFM and MEP. To the best of our knowledge, this is the first report to assess the concentrations of CPFM and its metabolite TCPY in an autopsy case.
Section snippets
Case history and autopsy findings
A 70-year-old man was found dead in his house and a cup containing a small amount of a solution with an irritant odor of agricultural chemicals was on the table near his body. An autopsy was performed approximately three days after his death. The man was relatively short (151 cm) and weighed 63.5 kg. There was no injury to the body.
Internal examinations revealed no injuries, diseases, or congenital malformations. In the air passage such as trachea and main bronchus, there was small amounts of
Results
Screening of the stomach contents of this case by GC–MS revealed CPFM and MEP, and their metabolites TCPY and 3MNP, respectively. Although xylene was also detected, a quantitative analysis was not performed.
CPFM, MEP, and MPP (IS) in heart blood extracts were separated using the DB-1MS column at retention times of 6.33, 6.52, and 6.69 min, respectively (Fig. 2). Calibration curves were linear between substance concentrations (Y) and peak area ratios (X, CPFM m/z 286/MPP m/z 278; MEP m/z 277/MPP m
Discussion
Few intoxication cases of CPFM have been reported in Japan. Only one autopsy case was described by Moriya and Hashimoto [17]. They found that blood concentrations (µg/mL) of CPFM were 1.01 (left cardiac chamber), 1.71 (right cardiac chamber), and 0.615 (right femoral vein). Based on these findings, the lower limit for a fatal blood level may be 0.6–1.7 µg/mL for CPFM poisoning. In this case, blood concentrations (µg/g) of CPFM were 27.8 (heart blood) and 6.60 (peripheral blood) (Table 2). These
Conflict of interest
The authors have no conflict of interest.
Acknowledgment
We thank Mr. Akira Minabe for his assistance.
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