Toxicity and carcinogenicity of N,N-dimethylformamide, a popular solvent in organic synthesis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F19%3A43918660" target="_blank" >RIV/60461373:22310/19:43918660 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Toxicity and carcinogenicity of N,N-dimethylformamide, a popular solvent in organic synthesis

Popis výsledku v původním jazyce

N,N-Dimethylformamide (DMF) is a dipolar aprotic solvent widely used in organic synthesis. It is known to cause alcohol intolerance at exposures as low as 15 mg/m3 (current occupational exposure limit), and increased markers of hepatotoxicity were reported in industrial workers exposed to DMF at average airborne concentrations below 30 mg/m3.1 DMF is readily absorbed through the skin. Dermal absorption can contribute as much as 71 % of the total DMF dose under conditions of actual occupational exposure.2 DMF has recently been classified by IARC as a probable human carcinogen (category 2A) based on limited evidence of carcinogenicity in humans and sufficient evidence in animals. The epidemiologic evidence came mainly from a cluster of testicular cancer cases in a group of aircraft repair workers who sprayed in-situ electrical cables with 80% DMF to dissolve the elastomeric surface coatings.3 However, the use of DMF as a solvent in organic chemistry laboratories appears to be sufficiently safe provided that proper precautions to minimise exposure are applied. Above all, skin contact should be avoided. Hepatotoxicity of DMF is linked to its metabolic activation to methylisocyanate and/or another carbamoylating species capable of covalent binding to proteins. In the ongoing project we are studying the formation and elimination of N-methylcarbamoyl adducts in globin with the aim to develop a new method for biological monitoring of cumulative internal exposure to DMF based on the analysis for cleavage products of globin adducts in the urine. Two of these cleavage products, N-methylcarbamoyl-valine and N-acetyl-N-methylcarbamoyllysine, which were found in the urine of both rats and humans, appear to be promising biomarkers of exposure to DMF.

Název v anglickém jazyce

Toxicity and carcinogenicity of N,N-dimethylformamide, a popular solvent in organic synthesis

Popis výsledku anglicky

N,N-Dimethylformamide (DMF) is a dipolar aprotic solvent widely used in organic synthesis. It is known to cause alcohol intolerance at exposures as low as 15 mg/m3 (current occupational exposure limit), and increased markers of hepatotoxicity were reported in industrial workers exposed to DMF at average airborne concentrations below 30 mg/m3.1 DMF is readily absorbed through the skin. Dermal absorption can contribute as much as 71 % of the total DMF dose under conditions of actual occupational exposure.2 DMF has recently been classified by IARC as a probable human carcinogen (category 2A) based on limited evidence of carcinogenicity in humans and sufficient evidence in animals. The epidemiologic evidence came mainly from a cluster of testicular cancer cases in a group of aircraft repair workers who sprayed in-situ electrical cables with 80% DMF to dissolve the elastomeric surface coatings.3 However, the use of DMF as a solvent in organic chemistry laboratories appears to be sufficiently safe provided that proper precautions to minimise exposure are applied. Above all, skin contact should be avoided. Hepatotoxicity of DMF is linked to its metabolic activation to methylisocyanate and/or another carbamoylating species capable of covalent binding to proteins. In the ongoing project we are studying the formation and elimination of N-methylcarbamoyl adducts in globin with the aim to develop a new method for biological monitoring of cumulative internal exposure to DMF based on the analysis for cleavage products of globin adducts in the urine. Two of these cleavage products, N-methylcarbamoyl-valine and N-acetyl-N-methylcarbamoyllysine, which were found in the urine of both rats and humans, appear to be promising biomarkers of exposure to DMF.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10406 - Analytical chemistry

Projekt

<a href="/cs/project/NV19-09-00378" target="_blank" >NV19-09-00378: Štěpné produkty proteinových aduktů v moči jako nový typ biomarkerů v preventivní medicíně</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů