An autopsy case of poisoning by massive absorption of cresol a short time before death

doi:10.1016/S0379-0738(02)00024-5

Forensic Science International

Volume 126, Issue 1, 28 March 2002, Pages 77-81

https://doi.org/10.1016/S0379-0738(02)00024-5 Get rights and content

Abstract

A 65-year-old male patient who was hospitalized with schizophrenia died about 15 min later after ingestion of a large volume of saponated cresol solution in a mental hospital. Fatal levels of free p- and m-cresol in the heart blood were detected at 458.8 and 957.3 μg/ml, respectively, which far exceeded the fatal levels determined previously. The levels in the heart muscle, liver and spleen tissues were also extremely high, and there was 250 ml of cresol-odor-emitting fluid in the stomach. The levels of glucuronic-acid-conjugated p- and m-cresols in the heart blood were 38.2 and 85.6 μg/ml, respectively. Although the high levels of cresols in the heart blood may be due to diffusion from the stomach contents, it is surmised that the essential levels of free and conjugated forms in blood were at least 99 and 240 μg/ml, respectively, considering the results of postmortem examinations and some case reports. It was concluded that about 340 μg/ml of the total cresols was absorbed in a very short period following oral ingestion of saponated cresol solution in this case.

Introduction

Saponated cresol, which is used as a disinfectant and insecticide, is a solution of approximately 50% cresol in saponified linseed oil, sodium or potassium hydroxide and water [1], [2]. Cresol is a mixture of the three isomers of methylphenol, in which the meta-isomer predominates, and is closely related chemically to phenol. After absorption through the skin and mucous membranes, it is metabolized by conjugation and oxidation [3]. Concentrated cresol denatures and precipitates cellular proteins and thus poisons all cells directly. Therefore, cresol may cause gastrointestinal corrosive injury, necrosis of the mucous membranes, cerebral edema, and degenerative changes in the liver and kidney following intoxication [4]. It was reported that the lethal dose of saponated cresol is approximately 60–120 ml, and the blood cresol level is 71–190 μg/ml [5], [6]. In the present report, we describe the case of an in-patient who died after ingestion of a large volume of saponated cresol solution in a mental hospital.

Section snippets

Case history

A 65-year-old male schizophrenic patient had been confined in a mental hospital for 12 years. He was kept in an isolation ward at night because of the seriousness of his case and violence. One morning, after his room had been soiled by his stools, a male nurse cleaned up the room with diluted saponated cresol solution between 10:00 and 11:00 a.m. The in-patient was given a bath and escorted to his room without clothes at 11:00 a.m. Afterward, the male nurse locked both the inside and outside

Autopsy findings

A judicial autopsy was performed about 27 h later. The body was 155 cm tall and weighed 43.0 kg. Rigor mortis was present in the joints of the extremities. There was a cresol-like odor around the cadaver. He had a chemical-burn-like dark brown color on the lips and around the mouth, over the chin, on the left side of the neck, the mid-sternal and left lateral sternal lines with branches, the left side of the abdomen and the back, and the gluteal regions, as shown in Fig. 1. The mucosa of the

Toxicological studies

The samples used for analyzing cresols were the remaining saponated cresol solution found in the patient’s room, the stomach contents, heart blood and urine, and some tissues collected at autopsy. These samples were kept at −40 °C until analysis. One hundred microliters each of the remaining saponated cresol solution, blood and urine was diluted to 1 ml with water. The diluted samples were acidified with 0.2 ml of 1N HCl and 2 ml of methylene chloride was added to the acidified samples for

Results and discussion

The total ion chromatogram and the EI-mass spectra of authentic cresols analyzed by GC–MS are shown in Fig. 2. Each isomer of cresol was almost separated, and the base peak ions of o-, m- and p-cresol were at m/z 108, 108 and 107, respectively. The retention times and the EI-mass spectra of authentic cresols were similar to those of m- and p-cresols in the remaining saponated cresol solution in the bottle, the stomach contents, heart blood and urine collected at autopsy. The o-cresol was not

References (8)

S.C. Hanvey, Antiseptics and disinfectants, fungicides, ectoparasiticides, in: A.G. Gilman, T.W. Rall, A.S. Nies, et...
M.J. Ellenhorn. Antiseptics and disinfectants, in: Ellenhorn’s Medical Toxicology, 2nd Edition, Williams and Wilkins,...
Analytical and toxicological data, in: A.C. Moffat, J.V. Jackson, M.S. Moss, B. Widdop (Eds.), Clarke’s Isolation and...
Antiseptics in: R.H. Dreisbach, (Ed.), Handbook of Poisoning: Prevention Diagnosis and Treatment, 11th Edition, Lauge...

There are more references available in the full text version of this article.

Cited by (19)

In-situ synchrotron imaging, experimental, and computational investigations on the efficiency of Trametes versicolor laccase on detoxification of P-Cresyl Sulfate (PCS) Protein Bound Uremic Toxin (PBUT)
2023, Journal of Biotechnology
Protein bound uremic toxins (PBUTs) are small substances binding to larger proteins, mostly human serum albumin (HSA), and are challenging to remove by hemodialysis (HD). Among different classes of PBUTs, p-cresyl sulfate (PCS) is the most widely used marker molecule and major toxin, as 95 % is bound to HSA. PCS has a pro-inflammatory effect and increases both the uremia symptom score and multiple pathophysiological activities. High-flux HD to clear PCS leads to serious loss of HSA, which results in a high mortality rate. The goal of the present study is to investigate the efficacy of PCS detoxification in serum of HD patients using a biocompatible laccase enzyme from Trametes versicolor. Molecular docking was used to gain an in-depth understanding of the interactions between PCS and the laccase to identify the functional group(s) responsible for ligand-protein receptor interactions. UV-Vis spectroscopy and gas chromatography-mass spectrometry (GC-MS) were used to assess the detoxification of PCS. GC-MS was used to identify the detoxification byproducts and their toxicity was assessed using docking commutations. In situ synchrotron radiation micro-computed tomography (SR-µCT) imaging available at the Canadian Light Source (CLS) was conducted to assess HSA binding with PCS before and after detoxification with laccase and undertake the corresponding quantitative analysis. GC-MS analyses confirmed the detoxification of PCS with laccase at a concentration of 500 mg/L. The potential pathway of PCS detoxification in the presence of the laccase was identified. Increasing laccase concentration led to the formation of m-cresol, as indicated by the corresponding absorption in the UV-Vis spectra and a sharp peak on the GC-MS spectra. Our analysis provides insight into the general features of PCS binding on Sudlow site II, as well as insights into PCS detoxification product interactions. The average affinity energy for detoxification products was lower than that of PCS. Even though some byproducts showed potential toxicity, the level was lower than for PCS based on toxicity indexes (e.g., LD50/LC50, carcinogenicity, neurotoxicity, mutagenicity). In addition, these small compounds can also be more easily removed by HD compared to PCS. SR-µCT quantitative analysis showed adhesion of the HSA to a significant reduced extent in the presence of the laccase enzyme in bottom sections of the polyarylethersulfone (PAES) clinical HD membrane tested. Overall, this study opens new frontiers for PCS detoxification.
Application of hydroxyapatite adsorbent packed in needle trap device for sensitive determination of trace levels of phenolic compounds in the air
2021, Chinese Journal of Analytical Chemistry
Citation Excerpt :
Phenolic compounds as petrochemical products possess an aromatic ring with one or more hydroxyl groups, and their structural complexity may be ranged from a simple phenolic molecule to a high molecular weight polymer. These compounds have wide applications as a disinfectant or part of disinfectant compounds and are important precursors of rubber and plastics, epoxy polycarbonates, nylon, detergents, and herbicides industries [1–3]. Excessive exposure to phenolic compounds may leads to adverse health effects such as eye irritation, headache, central nervous system paralysis, and protein degeneration.
Hydroxyapatites have been known as high adsorption capacity, inexpensive, and available absorbents. In this study, nano-hydroxyapatite (n-HA) adsorbent was synthesized, characterized, and employed as an efficient absorbent packed inside Needle Trap Device (NTD) as an environmentally friendly technique for sampling and analysis of phenolic compounds (phenol, 2-chlorophenol, o-cresol, and p-cresol) in the air. The effect of important parameters including the carryover, storage capability, repeatability, and reproducibility was investigated by Response Surface Methodology (RSM). The obtained results by the nano-hydroxyapatite packed NTD (nHAP-NTD) showed that the limit of detection and quantification of the studied analytes were in the range of 0.001–0.01 and 0.004–0.023 ng mL⁻¹, respectively. Also, the storage stability of the studied compounds in the nHAP-NTD was above 98% after 60 days at 4 °C. The finding results indicated a high correlation (R² = 0.98) between the proposed method (nHAP-NTD) and the XAD-7 sorbent tube (standard method NIOSH 2546). Finally, the proposed NTD-GC-FID method was successfully used to sample and determine the levels of the phenolic compounds in the real samples. The proposed nHAP-NTD method can be an eco-friendly, reliable, and efficient method for sampling and determination of the phenolic compounds compared to the National Institute for Occupational Safety and Health (NIOSH) method.
Autopsy report for chemical burns from cresol solution
2016, Experimental and Toxicologic Pathology
Citation Excerpt :
Corrosive poisons have historically been common suicidal agents, but are now relatively rarely used in advanced nations, probably due to the ease of access to less painful methods (Satoh et al., 2002; Saukko and Knight, 2004). Although cresol solution is easily available, few fatal cases have been reported in the medical literature (Monma-Ohtaki et al., 2002; Kinoshita et al., 2006). An octogenarian man suffering from depression was found dead in bed in his home.
Cresol, which is used as a disinfectant and insecticide, has erosive effects on epidermal and epithelial tissues in the body. Oral exposure causes gastrointestinal corrosive injuries as a direct chemical burn. We report herein a case of suicidal poisoning by ingestion of cresol solution. An octogenarian man with depression was found dead approximately 14 h after exposure to less than 500 mL of saponated cresol solution. Macroscopically, corrosive lesions such as red-to-brown-colored epithelium and edematous thickening of walls were seen in the skin, mouth, oral cavity, esophagus, and stomach. Histopathologically, coagulative necrosis and vascular dilatation were detected from mucosal to muscular layers in the esophagus, stomach, and duodenum. Congestive edema of the lungs, edematous changes in the brain, and proximal tubular necrosis of the kidneys were seen, suggesting acute circulatory disturbance due to shock. This human case offers valuable information on the direct irritation and shock induced by systemic exposure to corrosive substances.
Simultaneous oxidation of ammonium and p-cresol linked to nitrite reduction by denitrifying sludge
2012, Bioresource Technology
Citation Excerpt :
Specifically the phenolic compound, 4-methylphenol (p-cresol), is a natural product present in crude oil, foods, and is also detected in animal and human urine (Yan et al., 2005). The p-cresol exposition or ingestion can cause: (1) at high concentration, death (Monma-Ohtaki et al., 2002), (2) hepatotoxicity (Kamijo et al., 2003) and (3) the p-cresol in the human body is conjugated, with p-cresylsulphate as the main metabolite, the last cause toxic effects such as uremia (Schepers et al., 2007). Hence, it is of utmost importance to diminish the phenolic compound level in industrial effluents to tolerant limits prior to being released into the environment (Banerjee and Ghoshal, 2010).
The metabolic capability of denitrifying sludge to oxidize ammonium and p-cresol was evaluated in batch cultures. Ammonium oxidation was studied in presence of nitrite and/or p-cresol by 55 h. At 50 mg/L NH₄⁺-N and 76 mg/L NO₂⁻-N, the substrates were consumed at 100% and 95%, respectively, being N₂ the product. At 50 mg/L NH₄⁺-N and 133 mg/L NO₂⁻-N, the consumption efficiencies decreased to 96% and 70%, respectively. The increase in nitrite concentration affected the ammonium oxidation rate. Nonetheless, the N₂ production rate did not change. In organotrophic denitrification, the p-cresol oxidation rate was slower than ammonium oxidation. In litho-organotrophic cultures, the p-cresol and ammonium oxidation rates were affected at 133 mg/L NO₂⁻-N. Nonetheless, at 76 mg/L NO₂⁻-N the denitrifying sludge oxidized ammonium and p-cresol, but at different rate. Finally, this is the first work reporting the simultaneous oxidation of ammonium and p-cresol with the production of N₂ from denitrifying sludge.
Antiplatelet effect by p-cresol, a uremic and environmental toxicant, is related to inhibition of reactive oxygen species, ERK/p38 signaling and thromboxane A <inf>2</inf> production
2011, Atherosclerosis
Citation Excerpt :
This may partly explain the presence of hemorrhagic disorders and impairment of platelet aggregation in patients with cresol intoxication, severe uremia and hemolytic uremic syndrome [19,20]. p-cresol levels are about 100–250 μM in the plasma of uremic patients [2] and about 4.25 mM in heart blood of cresol poisoning cases [21], relatively higher than the p-cresol concentrations tested in our study. Moreover, uremic patients with daily hemodialysis further show inhibition of platelet function, prostaglandin metabolism and shear-induced platelet aggregation [11,22].
P-cresol is a well-known uremic toxin and environmental toxicant that may affect platelet functions. In this study, p-cresol (1–5 μM) inhibited the arachidonic acid (AA)-induced platelet aggregation, with 47% and 82% of inhibition at concentrations of 2 and 5 μM, respectively. Under similar experimental condition, p-cresol showed little effect on the U46619-induced platelet aggregation. p-cresol (<500 μM) revealed no discernable cytotoxicity to platelets as analyzed by quantification of lactate dehydrogenase release. Antiplatelet effect of p-cresol was related to inhibition of thromboxane A₂ (TXA₂) and prostaglandin D₂ (PGD₂) formation. P-cresol (2–100 μM) partly inhibited the AA-induced reactive oxygen species (ROS) production as well as the extracellular signal-regulated kinase (ERK1/2) and p38 phosphorylation in platelets. P-cresol further inhibited the AA-induced aggregation of rabbit platelet-rich plasma (PRP) with an IC50 of 2 μM and aggregation of human PRP (IC50 = 13.6 μM). Intravenous administration of p-cresol (250–1000 nmole) into mice effectively suppressed the ex vivo platelet aggregation, whereas showed little effect on the value of RBC, hemoglobin (HGB), hematocrit, MCV, MCH, MCHC, platelets and lymphocyte counts. These results indicate that in acute p-cresol-poisoning and long-term exposure to cresol as in severe uremic patients, p-cresol may potentially inhibit blood clot formation and lead to hemorrhagic disorders via inhibition of platelet aggregation, ROS production, ERK/p38 activation and TXA₂ production.
Carcinogenesis studies of cresols in rats and mice
2009, Toxicology
Cresols, monomethyl derivatives of phenol, are high production chemicals with potential for human exposure. The three isomeric forms of cresol are used individually or in mixtures as disinfectants, preservatives, and solvents or as intermediates in the production of antioxidants, fragrances, herbicides, insecticides, dyes, and explosives. Carcinogenesis studies were conducted in groups of 50 male F344/N rats and 50 female B6C3F1 mice exposed to a 60:40 mixture of m- and p-cresols (m-/p-cresol) in feed. Rats and mice were fed diets containing 0, 1500, 5000, or 15,000 ppm and 0, 1000, 3000, or 10,000 ppm, respectively. Survival of each exposed group was similar to that of their respective control group. Mean body weight gains were depressed in rats exposed to 15,000 ppm and in mice exposed to 3000 ppm and higher. A decrease of 25% over that of controls for the final mean body weight in mice exposed to 10,000 ppm appeared to be associated with lack of palatability of the feed. A marginally increased incidence of renal tubule adenoma was observed in the 15,000-ppm-exposed rats. The increased incidence was not statistically significant, but did exceed the range of historical controls. No increased incidence of hyperplasia of the renal tubules was observed; however, a significantly increased incidence of hyperplasia of the transitional epithelium associated with an increased incidence of nephropathy was observed at the high exposure concentration. The only significantly increased incidence of a neoplastic lesion related to cresol exposure observed in these studies was that of squamous cell papilloma in the forestomach of 10,000-ppm-exposed mice. A definitive association with irritation at the site-of-contact could not be made because of limited evidence of injury to the gastric mucosa at the time of necropsy. However, given the minimal chemical-related neoplastic response in these studies, it was concluded that there was no clear evidence of carcinogenicity in male rats or female mice exposed to the cresol mixture.

View all citing articles on Scopus

View full text

Case reportAn autopsy case of poisoning by massive absorption of cresol a short time before death