Limits...
Atypical bromethalin intoxication in a dog: pathologic features and identification of an isomeric breakdown product.

Bates MC, Roady P, Lehner AF, Buchweitz JP, Heggem-Perry B, Lezmi S - BMC Vet. Res. (2015)

Bottom Line: Bromethalin exposure and tissue absorption was confirmed by identification of one of two isomeric 543.7 molecular weight (MW) breakdown products in the patient's adipose and kidney samples using gas chromatography (GC) combined with tandem quadrupole mass spectrometry (MS/MS).Meningeal hemorrhages are atypical of bromethalin intoxication, and might have been caused by hyperthermia, secondary to tremors or hypernatremia.Identification of one of two isomeric breakdown products in the adipose tissue and kidney provides an additional molecule to the toxicologic testing regime for bromethalin intoxication.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Department of Pathobiology & Veterinary Diagnostic Laboratory, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL, 61802, USA. mbates@illinois.edu.

ABSTRACT

Background: Definitive post mortem confirmation of intoxication by the neurotoxic rodenticide bromethalin can be challenging. Brain lesions are not specific and detection of bromethalin and its metabolites are unpredictable due to rapid photodegradation and inconsistent behavior in tissues.

Case presentation: A 2-year-old dog presented with rapid onset of severe muscle tremors and death within hours after a known ingestion of a reportedly low dosage of bromethalin and subsequent decontamination using activated charcoal. Marked meningeal hemorrhages and multifocal myelin sheath vacuolation were observed in the brain. A marked reactive astrocytosis and neuronal hypoxia/necrosis were identified using immunohistochemistry (IHC) for glial fibrillary acidic protein (GFAP) and for neuron specific protein (NeuN). Bromethalin exposure and tissue absorption was confirmed by identification of one of two isomeric 543.7 molecular weight (MW) breakdown products in the patient's adipose and kidney samples using gas chromatography (GC) combined with tandem quadrupole mass spectrometry (MS/MS).

Conclusions: The severity of clinical signs and subsequent death of this dog was not expected with the low dosage of bromethalin reportedly ingested, and the use of activated charcoal possibly precipitated a hypernatremic status. Meningeal hemorrhages are atypical of bromethalin intoxication, and might have been caused by hyperthermia, secondary to tremors or hypernatremia. Identification of one of two isomeric breakdown products in the adipose tissue and kidney provides an additional molecule to the toxicologic testing regime for bromethalin intoxication.

No MeSH data available.


Related in: MedlinePlus

Likely origin of the two different 543.7 MW (nominal MW 541) bromethalin breakdown products as dehydrofluorodesmethylbromethalin structures of formula C13H4N3O4F2Br3. The compounds have been given common names of dehydrofluorodesmethylbromethalin-I and –II, which would be 6-(difluoromethylene)-2,4-dinitro-N-(2,4,6-tribromophenyl)cyclohexa-2,4-dien-1-imine and 8,8-difluoro-3,5-dinitro-(2,4,6-tribromophenyl)-7-azabicyclo[4.2.0]octa-1,3,5-triene, respectively. Dehydrofluorobromethalin (3,3-difluoro-5,7-dinitro-1-(2,4,6-tribromophenyl)indoline) was not seen and its absence is significant in light of the apparent lack of formation of a five member ring in deference to a more constrained four member ring
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4584469&req=5

Fig4: Likely origin of the two different 543.7 MW (nominal MW 541) bromethalin breakdown products as dehydrofluorodesmethylbromethalin structures of formula C13H4N3O4F2Br3. The compounds have been given common names of dehydrofluorodesmethylbromethalin-I and –II, which would be 6-(difluoromethylene)-2,4-dinitro-N-(2,4,6-tribromophenyl)cyclohexa-2,4-dien-1-imine and 8,8-difluoro-3,5-dinitro-(2,4,6-tribromophenyl)-7-azabicyclo[4.2.0]octa-1,3,5-triene, respectively. Dehydrofluorobromethalin (3,3-difluoro-5,7-dinitro-1-(2,4,6-tribromophenyl)indoline) was not seen and its absence is significant in light of the apparent lack of formation of a five member ring in deference to a more constrained four member ring

Mentions: In the adipose and kidney samples provided for this case, a 543.7 MW breakdown product of molecular formula C13H4N3O4F2Br3 provided analytical evidence for bromethalin exposure (Fig. 3b,c). Figure 4 illustrates the likely origin of the two different 543.7 MW (nominal MW 541) bromethalin breakdown products. Both liver and brain were negative for bromethalin, desmethylbromethalin, and either breakdown product. Novel peaks were assigned by inference that compounds with tribrominated isotopic abundance patterns surrounding the molecular ion could only have arisen from bromethalin either in standards of bromethalin or in spiked liver samples (spectra not shown).Fig. 4


Atypical bromethalin intoxication in a dog: pathologic features and identification of an isomeric breakdown product.

Bates MC, Roady P, Lehner AF, Buchweitz JP, Heggem-Perry B, Lezmi S - BMC Vet. Res. (2015)

Likely origin of the two different 543.7 MW (nominal MW 541) bromethalin breakdown products as dehydrofluorodesmethylbromethalin structures of formula C13H4N3O4F2Br3. The compounds have been given common names of dehydrofluorodesmethylbromethalin-I and –II, which would be 6-(difluoromethylene)-2,4-dinitro-N-(2,4,6-tribromophenyl)cyclohexa-2,4-dien-1-imine and 8,8-difluoro-3,5-dinitro-(2,4,6-tribromophenyl)-7-azabicyclo[4.2.0]octa-1,3,5-triene, respectively. Dehydrofluorobromethalin (3,3-difluoro-5,7-dinitro-1-(2,4,6-tribromophenyl)indoline) was not seen and its absence is significant in light of the apparent lack of formation of a five member ring in deference to a more constrained four member ring
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4584469&req=5

Fig4: Likely origin of the two different 543.7 MW (nominal MW 541) bromethalin breakdown products as dehydrofluorodesmethylbromethalin structures of formula C13H4N3O4F2Br3. The compounds have been given common names of dehydrofluorodesmethylbromethalin-I and –II, which would be 6-(difluoromethylene)-2,4-dinitro-N-(2,4,6-tribromophenyl)cyclohexa-2,4-dien-1-imine and 8,8-difluoro-3,5-dinitro-(2,4,6-tribromophenyl)-7-azabicyclo[4.2.0]octa-1,3,5-triene, respectively. Dehydrofluorobromethalin (3,3-difluoro-5,7-dinitro-1-(2,4,6-tribromophenyl)indoline) was not seen and its absence is significant in light of the apparent lack of formation of a five member ring in deference to a more constrained four member ring
Mentions: In the adipose and kidney samples provided for this case, a 543.7 MW breakdown product of molecular formula C13H4N3O4F2Br3 provided analytical evidence for bromethalin exposure (Fig. 3b,c). Figure 4 illustrates the likely origin of the two different 543.7 MW (nominal MW 541) bromethalin breakdown products. Both liver and brain were negative for bromethalin, desmethylbromethalin, and either breakdown product. Novel peaks were assigned by inference that compounds with tribrominated isotopic abundance patterns surrounding the molecular ion could only have arisen from bromethalin either in standards of bromethalin or in spiked liver samples (spectra not shown).Fig. 4

Bottom Line: Bromethalin exposure and tissue absorption was confirmed by identification of one of two isomeric 543.7 molecular weight (MW) breakdown products in the patient's adipose and kidney samples using gas chromatography (GC) combined with tandem quadrupole mass spectrometry (MS/MS).Meningeal hemorrhages are atypical of bromethalin intoxication, and might have been caused by hyperthermia, secondary to tremors or hypernatremia.Identification of one of two isomeric breakdown products in the adipose tissue and kidney provides an additional molecule to the toxicologic testing regime for bromethalin intoxication.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Department of Pathobiology & Veterinary Diagnostic Laboratory, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL, 61802, USA. mbates@illinois.edu.

ABSTRACT

Background: Definitive post mortem confirmation of intoxication by the neurotoxic rodenticide bromethalin can be challenging. Brain lesions are not specific and detection of bromethalin and its metabolites are unpredictable due to rapid photodegradation and inconsistent behavior in tissues.

Case presentation: A 2-year-old dog presented with rapid onset of severe muscle tremors and death within hours after a known ingestion of a reportedly low dosage of bromethalin and subsequent decontamination using activated charcoal. Marked meningeal hemorrhages and multifocal myelin sheath vacuolation were observed in the brain. A marked reactive astrocytosis and neuronal hypoxia/necrosis were identified using immunohistochemistry (IHC) for glial fibrillary acidic protein (GFAP) and for neuron specific protein (NeuN). Bromethalin exposure and tissue absorption was confirmed by identification of one of two isomeric 543.7 molecular weight (MW) breakdown products in the patient's adipose and kidney samples using gas chromatography (GC) combined with tandem quadrupole mass spectrometry (MS/MS).

Conclusions: The severity of clinical signs and subsequent death of this dog was not expected with the low dosage of bromethalin reportedly ingested, and the use of activated charcoal possibly precipitated a hypernatremic status. Meningeal hemorrhages are atypical of bromethalin intoxication, and might have been caused by hyperthermia, secondary to tremors or hypernatremia. Identification of one of two isomeric breakdown products in the adipose tissue and kidney provides an additional molecule to the toxicologic testing regime for bromethalin intoxication.

No MeSH data available.


Related in: MedlinePlus