Nitrosamines toxicity

Sodium Nitrate and Sodium Nitrite. Nitrates and nitrites ate used in meat-curing processes to prevent the growth of bacteria that cause botulism. Nitrates have been shown to form low, but possibly toxic, levels of nitrosamines in certain cured meats. For this reason, the safety of these products has been questioned, and use is limited (80). 

Toxicity. Many /V-nitrosamines are toxic to animals and cells in culture (4,6—8,88). /V-Nitrosodimethy1amine [62-75-9] (NDMA) is known to be acutely toxic to the Hver in humans, and exposure can result in death (89). Liver damage, diffuse bleeding, edema, and inflammation are toxic effects observed in humans as a result of acute and subacute exposure to NDMA. These effects closely resemble those observed in animals dosed with NDMA (89,90). 

Thiuram Sulfides. These compounds, (8) and (9), are an important class of accelerator. Thiurams are produced by the oxidation of sodium dithiocarbamates. The di- and polysulfides can donate one or more atoms of sulfur from their molecular stmcture for vulcanization. The use of these compounds at relatively high levels with litde or no elemental sulfur provides articles with improved heat resistance. The short-chain (methyl and ethyl) thiurams and dithiocarbamates ate priced 2/kg. Producers have introduced ultra-accelerators based on longer-chain and branched-chain amines that are less volatile and less toxic. This development is also motivated by a desire to rninirnize airborne nitrosamines. 

Care must be exercised in using sodium nitrite near other chemicals. It is incompatible with ammonium salts, thiocyanates, thiosulfates, and strong reducing agents. In acid solutions, sodium nitrite evolves toxic NO in the presence of secondary amines it can form nitrosamines which are suspected carcinogens. 

The functions of nitrite and the formation of volatile N-nitrosamines in food systems and their toxicity have been well... 

Conversion of a nontoxic molecule to one that is toxic, or a molecule with low potency to one that is more potent. Examples include the formation of the phenoxy herbicide 2,4-D from the corresponding butyrate, formation of nitrosamines, and methylation of arsenicals to trimethylarsine. 

It is accepted that many widely used latex vulcanisation accelerators - dithiocaibamates, thiurams and thiazoles - are capable of producing Type IV allergic response in certain individuals within the population and may also possess increasingly unacceptable eco-toxic and acute toxicity profiles. Thiurams and dithiocaibamates (derived from secondary amines) can also produce potentially harmful N-nitrosamines. Four safer accelerators developed and commercialised by Robinson Brothers are described. They are designed to reduce or eliminate the impact of the above problems using sustainable technology. At the same time these accelerators produce equivalent technological performances to those conventionally used. 10 refs. 

Consideration is given to the toxicity of nitrosamines formed during rubber vulcanisation in the presence of certain accelerators, the mechanisms by which they are formed, and French, German and European Union regulations relating to nitrosamines in the workplace atmosphere and in rubber products. Methods used in the sampling and analysis of nitrosamines are also described. 6 refs. 

The various effects of the Toxic Substances Control Act (TSCA) on the metalworking fluids Industry is presented, with emphasis placed on nitrosamine contamination of the fluids. A review of the literature on the effects of various metalworking fluid additives on nitrosamine formation is also presented to aid the industry in dealing with the nuisance of nitrosamine contamination. It is concluded that with increased awareness of nitrosamine contamination as a result of the implementation of TSCA and careful consideration of the factors described in this paper, it may be possible to design and control a nitrosamine-free metalworking fluid. 

The nitrolysis of nitrosamines has been relatively unexplored because of the high toxicity of such substrates. Atkins and Willer have prepared a number of cyclic 1,3-dinitrosamines... 

In view of the highly carcinogenic nature of many nitrosamines any experiments involving their isolation must be discouraged, and for this reason, this section has only been written for completeness. This high toxicity is unfortunate because the preparation of nitrosamines from the parent amines is often facile and they provide a route to highly pure nitramines. Other equally useful methods for the synthesis of nitramines, such as the chloride-catalyzed nitration of secondary amines, also suffer from the formation of nitrosamines in appreciable amounts and must also be viewed with caution. 

Interactions between chemicals may be of a physico-chemical and/or biological nature. Examples of physico-chemical interactions are the reaction of nitrite with aUcylamines to produce carcinogenic nitrosamines, and the binding of toxic chemicals to active charcoal resulting in a decreased absorption from the gastrointestinal tract. It is held that physico-chemical interactions will normally only occur at high doses and therefore are of lesser importance for low-dose scenarios. Physico-chemical interactions will therefore not be considered in any detail in this book. 

As seen in Figure 13-24, secondary amines react directly with acidic sodium nitrite to form a nitrosamine. (These compounds are very, very toxic.) Primary amines react under similar conditions to form unstable diazonium salts (see Figure 13-25). Diazonium salts readily lose the very stable N2 to form reactive carbocations that are useful in a number of synthetic pathways. Figure 13-26 shows the resonance stabilization of a diazonium ion. 

This equation is a fairly typical biological structure-activity relationship with a strong dependence on partition coefficients, and it therefore suggests that the nitrosamines, and perhaps other chemical carcinogens as well, are similar - in the pharmacological sense - to analgesics or toxic agents. 

Grosjean, D Atmospheric Chemistry of Toxic Contaminants. 6. Nitrosamines Dialkyl Nitrosamines and Nitrosomorpholine, J. Air Waste Manage. Assoc., 41, 306-311 (1991d). 

The existence of "no-effect doses" for toxic compounds is a controversial point, but it is clear that to measure the exposure sufficiently accurately and to detect the response reliably are major problems (see below for further discussion). Suffice it to say that certain carcinogens are carcinogenic after exposure to concentrations measured in parts per million, and the dose-response curves for some nitrosamines and for ionizing radiation appear to pass through zero when the linear portion is extrapolated. At present, therefore, in some cases no-effect levels cannot be demonstrated for certain types of toxic effect. 

Nitrous acid, formed from organic precursors such as nitrosamines and from nitrite and nitrate salts, is a potent accelerator of the deamination of bases. Bisulfite has similar effects. Both agents are used as preservatives in processed foods to prevent the growth of toxic bacteria. They do not appear to increase cancer risks... 

Nitrosamines are toxic compounds as well as potent animal and human carcinogens (Patnaik, 1992). These substances occur in trace quantities in tobacco smoke, meat products, and salted fish. Some of these compounds are classified by U.S. EPA as priority pollutants in industrial wastewaters, potable waters, and hazardous wastes. These nitrosamines are listed in Table 2.16.1. Such pollutants occurring in environmental samples can be determined by U.S. EPA s analytical procedures (U.S. EPA 1990, 1992). 

Draper III, A.C. and Brewer, W.S. (1979) Measurement of the aquatic toxicity of volatile nitrosamines, Journal of Toxicology and Environmental Health 5 (6), 985-993. 

Variations in the use pattern of industrial and agricultural chemicals throughout the world preclude standardization by international organizations such as OECD. Despite this fact, common dietary constituents, which are known to influence toxicity are antioxidants, unsaturated fatty acids, and selenium. These must be present in interfering concentrations. The potential impact of several common dietary contaminants on chronic toxicity assessment therefore, necessitates that special attention be given to their presence. In this respect, substances of concern include pesticide residues, chlorinated and polycyclic aromatic hydrocarbons, estrogens, heavy metals, nitrosamines, and mycotoxins. 

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