3-Butenenitrile: Occurrence, Metabolism and Health Effects

General Description

3-Butenenitrile, a naturally occurring compound, is crucial in industrial processes and surgical settings. Its metabolism involves enzymatic pathways leading to toxic byproducts like hydrogen cyanide. While its health impacts on humans are not extensively documented, exposure risks exist for certain occupations and through consumption of cruciferous plants. Research suggests that subtoxic exposure to 3-Butenenitrile can enhance enzyme activities, potentially through Nrf2 activation, offering protection against neurotoxicity and inflammation. Further studies are needed to fully understand its effects on redox balance and antioxidant activities, highlighting the need for ongoing research in this area.

Figure 1. 3-Butenenitrile

Occurrence

3-butenenitrile, a naturally occurring organic compound, is commonly found in the environment. 3-butenenitrile serves a crucial role in various industrial processes as it is extensively utilized in the production of plastics, solvents, and synthetic intermediates. The thermal breakdown of acrylonitrile-based plastics results in the release of a diverse range of nitriles, among which allyl nitrile is prominent. Notably, 3-butenenitrile has been identified as a component of smoke produced during surgical procedures involving lasers and electro-surgical units. Although there have been reports detecting 3-butenenitrile in the environment, quantitative data remains limited, and there is a lack of literature documenting its direct health impacts on humans. However, individuals working in occupations where exposure to allyl nitrile is possible may face certain risks. Additionally, 3-butenenitrile is naturally produced by cruciferous plants, suggesting that consumption of such plants could also lead to exposure to this nitrile. Overall, 3-butenenitrile's occurrence spans from industrial settings to natural sources, highlighting its significance and potential implications for human health. ¹

Metabolism

The metabolism of 3-butenenitrile involves a series of enzymatic reactions in the body. Upon ingestion, 3-butenenitrile is believed to undergo two main metabolic pathways. First, it is thought to undergo α-carbon hydroxylation mediated by the cytochrome P450 (CYP) 2E1 enzyme, which results in the formation of an unstable cyanohydrin. This cyanohydrin subsequently decomposes into 2-propenal (acrolein) and hydrogen cyanide. The formation of hydrogen cyanide contributes to the acute toxicity associated with allyl nitrile. Secondly, 3-butenenitrile can undergo epoxidation of the β-γ double bond, a process catalyzed by the enzyme CYP2A5 in mice (the human ortholog being CYP2A6). This leads to the formation of 3,4-epoxybutyronitrile. The epoxide can then be further metabolized into 3,4-dihydroxybutyronitrile through epoxide hydrolase activity, or it can form a glutathione conjugate through a reaction with glutathione (GSH). The resulting metabolites, such as the epoxide and its derivatives, are thought to contribute to the biological activities and toxic effects exhibited by allyl nitrile. Specifically, the epoxide has been implicated in the vestibulotoxicity associated with 3-butenenitrile. Further research is needed to fully understand the specific bioactivities and toxicological mechanisms associated with the various metabolites of 3-butenenitrile. This information is crucial for a comprehensive understanding of the impact of 3-butenenitrile on human health and for the development of potential interventions to mitigate its adverse effects. ²

Health effects

3-Butenenitrile has been studied for its health effects, particularly its impact on redox balance and antioxidant/phase II enzyme activities in the body. Research has shown that exposure to subtoxic levels of 3-Butenenitrile can enhance the activities of various important enzymes such as glutathione S-transferase, quinone reductase, glutathione peroxidase, and superoxide dismutase, while reducing the activities of catalase and glutathione reductase in different tissues including the gastrointestinal tract, kidneys, lungs, urinary bladder, and brain. Studies have indicated that 3-Butenenitrile may exert its effects through the activation of nuclear factor erythroid 2-related factor-2 (Nrf2) due to the conversion of 3-Butenenitrile to electrophilic metabolites. Furthermore, research has shown that repeated exposure to allyl nitrile at subtoxic levels can protect against neurotoxicity and inflammation. For instance, pre-treatment with 3-Butenenitrile led to elevated antioxidant and phase II enzyme activities in the brain, contributing to protection against neurotoxicity. Additionally, repeated exposure to 3-Butenenitrile reduced edema induced by certain sensitizers and decreased oxidative stress markers, suggesting a potential protective role against skin sensitization. Overall, further studies are needed to fully understand the mechanisms by which allyl nitrile influences antioxidant enzyme activities and its potential protective effects against occupational chemicals. These findings highlight the complex interplay between 3-Butenenitrile and redox balance in the body, emphasizing the importance of continued research in this area. ²

Reference

1. Shapi MM, Hesso A. Gas chromatographic-mass spectrometric analysis of some potential toxicants amongst volatile compounds emitted during large-scale thermal degradation of poly(acrylonitrile-butadiene-styrene) plastic. J Chromatogr. 1991;562(1-2):681-696.

2. Tanii H. Allyl nitrile: Toxicity and health effects. J Occup Health. 2017;59(2):104-111.