2,6-Dimethylaniline--hemoglobin adducts from lidocaine in humans.

doi:10.1093/CARCIN/15.10.2287

Paper

2,6-Dimethylaniline--hemoglobin adducts from lidocaine in humans.

Published Oct 1, 1994 · M. Bryant, H. J. Simmons, R. E. Harrell

Carcinogenesis

Q1 SJR score

44

Citations

1

Influential Citations

Full textSemantic Scholar

Abstract

Lidocaine (xylocaine) is utilized for the treatment of ventricular arrhythmias which occur during cardiac surgery or myocardial infarction and as a local anesthetic. Recent data from the National Toxicology Program reported that a principal metabolite in man, 2,6-dimethylaniline, is carcinogenic in rats. In addition, the putative metabolite N-hydroxy-2,6-dimethylaniline has been reported to be mutagenic in Salmonella typhimurium TA100. N-Hydroxy metabolites of aromatic amines may be oxidized by hemoglobin to the corresponding nitroso metabolites and the nitroso may covalently bind to cysteine groups in hemoglobin as the corresponding sulfinic acid amide. Since hemoglobin binding is an indirect measure of the formation of the N-hydroxy metabolite, we have examined the possibility that lidocaine or a metabolite may similarly covalently bind to hemoglobin in rats and humans. Using a previously developed gas chromatographic-mas spectrometric assay, hemoglobin adducts of 2,6-dimethylaniline were detected covalently bound to rat hemoglobin after administration of either 2,6-dimethylaniline or lidocaine. Consistent with previously reported observations, low levels of 2,6-dimethylaniline-hemoglobin adducts were also observed in human subjects before lidocaine administration. Following administration of lidocaine, all patients had much higher levels of 2,6-dimethylaniline-hemoglobin adducts. Differences in adduct levels in patients treated with lidocaine (70-3760 mg) ranged from 93 to 636 ng/g hemoglobin. These data indicate that N-hydroxy-2,6-dimethylaniline is a metabolite of lidocaine in man.

Non-RCT

Study Snapshot

N-hydroxy-2,6-dimethylaniline is a metabolite of lidocaine in humans, potentially causing carcinogenic effects in rats and mutagenic effects in Salmonella typhimurium TA100.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

2,6-Dimethylaniline--hemoglobin adducts from lidocaine in humans.

Sign up to use Study Snapshot

References

Citations

Aromatic amines leachate from cigarette butts into aquatic environments: Is there risk for water organisms?

Cigarette butts release aromatic amines, which pose medium risks to sensitive crustaceans and fish, necessitating restrictions on littering.

Effect of 2,6-xylidine (DMA) on secretion of biomarkers for inflammation and neurodevelopment by the placenta.

DMA, a component of cigarette smoke, may interfere with placental steroidogenesis and enhance placental inflammation, potentially increasing the risk of adverse pregnancy outcomes.

A weight of evidence assessment of the genotoxicity of 2,6-xylidine based on existing and new data, with relevance to safety of lidocaine exposure.

2,6-xylidine is not genotoxic in vivo in rats without acute systemic toxic effects, indicating it is not a direct acting genotoxin.

Preclinical safety assessment of antipyrine combined with lidocaine hydrochloride as ear drops

Antipyrine combined with lidocaine hydrochloride ear drops show no obvious skin sensitization or irritation toxicity, but may cause side effects in the blood and digestive systems.

Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays

Carcinogenic activities of dimethylaniline isomers are associated with mutagenic events in mice, with 2,5-DMA and 2,6-DMA showing increased mutation frequencies in nasal tissues.