ABSTRACT

N-Nitroso compounds (NOCs) were originally synthe-

sized about 100 years ago by reacting secondary

amines with nitrous acid. They were used by various

industries as solvents until their toxicity was discovered

in 1937. Freund (1) was the original discoverer of the

toxicity of NOCs in 1937 and reported that animals

such as mice and dogs exposed to N-nitrosodimethyl-

amine (NDMA) vapors develop liver necrosis. An

extensive investigation by Barnes and Magee (2) also

found that NDMA is acutely hepatotoxic. Two years

later, the same workers (3) showed that liver tumors

could be induced in rats by feeding them NDMA. This

research into the carcinogenicity of NOCs was pub-

lished in 1956 and triggered intense research into the

biological effects of NOCs. The suspicion that NOCs might be contained in

foods resulted from studies carried out in Norway

in the late 1950s. Ender et al. (4) found that liver

disorders in mink and several ruminants were related

to the feeding of nitrite-preserved herring meal. The

toxic component of the herring meal was then isolated

and identified as NDMA and it was suggested that

NDMA may result from the reaction of dimethylamine

(DMA) in fish meal with nitrous acid derived from the

sodium nitrite preservative (5). These seminal studies

prompted researchers to examine human foods for

the presence of NOCs. Since the middle of the 1960s,

many human foods have been analyzed and several

have been found to contain NOCs (6-9). From the

early 1970s, the literature concerning the analysis,

detection, and synthesis of NOCs expanded consider-

ably and resulted in the proceedings from meetings

that were held in 1971 and again in 1973 at the

International Agency for Research on Cancer (IARC). To detect NOCs in foods, methods involving the

precise gas chromatography (GC)–mass spectrometry

(MS) technique were developed by a large number of

investigators (10-14). Subsequently, a thermal-energy

analyzer (TEA) was found to be superior to other GC

detectors in detecting NOCs in foods, beverages, and

complex biological mixtures due to its high sensitivity

and selectivity. Currently, the most frequently used

method for detecting N-nitrosamines (NAs) is GC-

TEA and high-performance liquid chromatography

(HPLC)–TEA.