Cyanide Toxicokinetics: The Behavior of Cyanide, Thiocyanate and 2-Amino-2-Thiazoline-4-Carboxylic Acid in Multiple Animal Models

Bhandari, Raj K.; Oda, Robert P.; Petrikovics, Ilona; Thompson, David E.; Brenner, Matthew; Mahon, Sari B.; Bebarta, Vikhyat S.; Rockwood, Gary A.; Logue, Brian A.

doi:10.1093/jat/bku020

Cited by 57 publications

(37 citation statements)

References 30 publications

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“…These concentrations deviated by less than 3.5% of the concentrations found by LC–MS/MS (Figure 6A). Similar to observations of Bhandari et al, 19 blood cyanide concentrations exhibited a linear response to increasing doses of cyanide (Figure 6B). Each rabbit that could be considered “exposed” (i.e., CN concentration levels above 10 µM) was correctly diagnosed from the analysis of whole blood by the sensor.…”

Section: Resultssupporting

confidence: 89%

“…Rabbit blood drawn prior to exposure produced a small amount of fluorescence due to endogenous cyanide concentrations, 19,38 but it was below the LOD. Rabbit blood drawn at 15, 25, and 35 min into the infusion period produced cyanide concentrations of 35.6 ± 4.8, 49.7 ± 8.2, and 74.6 ± 15.6 µM, respectively, as measured by the sensor.…”

Section: Resultsmentioning

confidence: 99%

“…18 ATCA has only recently been suggested for use as a biomarker, but it accounts for up to 20% of cyanide metabolism, with an increase in ATCA production as cyanide dose increases. 3,19 Although SCN − is a valuable marker of cyanide exposure, metabolism of cyanide to thiocyanate is enzymatically rate limited 20 and maximum thiocyanate concentrations can lag maximum cyanide concentrations by approximately 20 min to 6 h. 21 Although ATCA mirrors the behavior of cyanide, 19 its concentration in plasma has been found to be relatively low, necessitating an extremely sensitive diagnostic analysis.…”

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confidence: 99%

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Development of a Fluorescence-Based Sensor for Rapid Diagnosis of Cyanide Exposure

et al. 2014

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Although commonly known as a highly toxic chemical, cyanide is also an essential reagent for many industrial processes in areas such as mining, electroplating, and synthetic fiber production. The “heavy” use of cyanide in these industries, along with its necessary transportation, increases the possibility of human exposure. Because the onset of cyanide toxicity is fast, a rapid, sensitive, and accurate method for the diagnosis of cyanide exposure is necessary. Therefore, a field sensor for the diagnosis of cyanide exposure was developed based on the reaction of naphthalene dialdehyde, taurine, and cyanide, yielding a fluorescent β-isoindole. An integrated cyanide capture “apparatus”, consisting of sample and cyanide capture chambers, allowed rapid separation of cyanide from blood samples. Rabbit whole blood was added to the sample chamber, acidified, and the HCN gas evolved was actively transferred through a stainless steel channel to the capture chamber containing a basic solution of naphthalene dialdehyde (NDA) and taurine. The overall analysis time (including the addition of the sample) was <3 min, the linear range was 3.13–200 µM, and the limit of detection was 0.78 µM. None of the potential interferents investigated (NaHS, NH4OH, NaSCN, and human serum albumin) produced a signal that could be interpreted as a false positive or a false negative for cyanide exposure. Most importantly, the sensor was 100% accurate in diagnosing cyanide poisoning for acutely exposed rabbits.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Development of a Fluorescence-Based Sensor for Rapid Diagnosis of Cyanide Exposure

et al. 2014

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“…Potassium cyanide disturbs mitochondrial energy metabolism by inhibiting mitochondrial cytochrome oxidase which then results in cellular hypoxia and cytotoxic anoxia and may eventually lead to death . The reason for the finding of this study that potassium cyanide was much more toxic in human BJ fibroblasts compared to the mouse BALB 3T3 fibroblasts is likely due to the species metabolism because at least animal species are known to metabolize cyanide differentially .…”

Section: Discussionmentioning

confidence: 75%

Human BJ Fibroblasts is an Alternative to Mouse BALB/c 3T3 Cells in In Vitro Neutral Red Uptake Assay

Mannerström

Toimela

Sarkanen

et al. 2017

Basic Clin Pharma Tox

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The OECD GD 129 BALB/c 3T3 neutral red uptake (NRU) assay is a standardized test method for estimating starting dose for an acute oral systemic toxicity test in rodents. Mouse BALB/c 3T3 fibroblasts are the most commonly used cells in the NRU assay. We have previously transferred and validated BALB/c 3T3 NRU assay in our GLP laboratory. Subsequently, in order to obtain more human-relevant cytotoxicity data, we performed an intralaboratory validation using human BJ fibroblasts in the NRU assay instead of mouse BALB/c 3T3 fibroblasts. Here, we present comparative cytotoxicity data of 26 different test chemicals (pharmaceuticals, industrial chemicals, pesticides and food additives) produced with both BALB/c 3T3 NRU and BJ NRU assays.

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“…This pathway accounts for about 15-20% of cyanide metabolism (Wood and Cooley, 1956). Thiocyanate and ATCA are chemically stable metabolites which are not further metabolised but excreted with the urine (Bhandari et al, 2014). Another detoxification pathway is the reaction of cyanide with endogenous a-ketoglutarate (a-KG) to form a-ketoglutarate cyanhydrin (a-KGCN).…”

Section: Laboratory Animalsmentioning

confidence: 99%

Acute health risks related to the presence of cyanogenic glycosides in raw apricot kernels and products derived from raw apricot kernels

Alexander

Barregård²,

Bignami³

et al. 2016

EFS2

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Amygdalin is the major cyanogenic glycoside present in apricot kernels and is degraded to cyanide by chewing or grinding. Cyanide is of high acute toxicity in humans. The lethal dose is reported to be 0.5-3.5 mg/kg body weight (bw). An acute reference dose (ARfD) of 20 lg/kg bw was derived from an exposure of 0.105 mg/kg bw associated with a non-toxic blood cyanide level of 20 micro mol (lM), and applying an uncertainty factor of 1.5 to account for toxicokinetic and of 3.16 to account for toxicodynamic inter-individual differences. In the absence of consumption data and thus using highest intakes of kernels promoted (10 and 60 kernels/day for the general population and cancer patients, respectively), exposures exceeded the ARfD 17-413 and 3-71 times in toddlers and adults, respectively. The estimated maximum quantity of apricot kernels (or raw apricot material) that can be consumed without exceeding the ARfD is 0.06 and 0.37 g in toddlers and adults, respectively. Thus the ARfD would be exceeded already by consumption of one small kernel in toddlers, while adults could consume three small kernels. However, consumption of less than half of a large kernel could already exceed the ARfD in adults.

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Cyanide Toxicokinetics: The Behavior of Cyanide, Thiocyanate and 2-Amino-2-Thiazoline-4-Carboxylic Acid in Multiple Animal Models

Cited by 57 publications

References 30 publications

Development of a Fluorescence-Based Sensor for Rapid Diagnosis of Cyanide Exposure

Development of a Fluorescence-Based Sensor for Rapid Diagnosis of Cyanide Exposure

Human BJ Fibroblasts is an Alternative to Mouse BALB/c 3T3 Cells in In Vitro Neutral Red Uptake Assay

Acute health risks related to the presence of cyanogenic glycosides in raw apricot kernels and products derived from raw apricot kernels

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