1,3-Butadiene: a ubiquitous environmental mutagen and its associations with diseases

Abstract

Abstract1,3-Butadiene (BD) is a petrochemical manufactured in high volumes. It is a human carcinogen and can induce lymphohematopoietic cancers, particularly leukemia, in occupationally-exposed workers. BD is an air pollutant with the major environmental sources being automobile exhaust and tobacco smoke. It is one of the major constituents and is considered the most carcinogenic compound in cigarette smoke. The BD concentrations in urban areas usually vary between 0.01 and 3.3 μg/m3 but can be significantly higher in some microenvironments. For BD exposure of the general population, microenvironments, particularly indoor microenvironments, are the primary determinant and environmental tobacco smoke is the main contributor. BD has high cancer risk and has been ranked the second or the third in the environmental pollutants monitored in most urban areas, with the cancer risks exceeding 10-5. Mutagenicity/carcinogenicity of BD is mediated by its genotoxic metabolites but the specific metabolite(s) responsible for the effects in humans have not been determined. BD can be bioactivated to yield three mutagenic epoxide metabolites by cytochrome P450 enzymes, or potentially be biotransformed into a mutagenic chlorohydrin by myeloperoxidase, a peroxidase almost specifically present in neutrophils and monocytes. Several urinary BD biomarkers have been developed, among which N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine is the most sensitive and is suitable for biomonitoring BD exposure in the general population. Exposure to BD has been associated with leukemia, cardiovascular disease, and possibly reproductive effects, and may be associated with several cancers, autism, and asthma in children. Collectively, BD is a ubiquitous pollutant that has been associated with a range of adverse health effects and diseases with children being a subpopulation with potentially greater susceptibility. Its adverse effects on human health may have been underestimated and more studies are needed.

Biohydrogenation of 1,3-Butadiene to 1-Butene under Acetogenic Conditions by Acetobacterium wieringae

“…106-99-0) for the synthesis of polymers (e.g., synthetic rubber and thermoplastic resins) has led to high demand and large-scale production of BD in the petrochemical industry. , According to the 2016 Chemical Data Reporting (), the annual production volume of BD in the United States was estimated to be between 1 and 5 billion lb (i.e., 0.45 to 2.27 × 10 6 tons). Uncontrolled emission, improper disposal, and accidental spillage have caused the detection of BD in soil, groundwater, surface water, and drinking water supplies, which pose detrimental effects threatening human health . BD has been identified in 17 of the 1867 U.S. Environmental Protection Agency (USEPA) National Priorities List (NPL) sites and is ranked 154 of 857 contaminants in the Substance Priority List .…”

“…BD has been identified in 17 of the 1867 U.S. Environmental Protection Agency (USEPA) National Priorities List (NPL) sites and is ranked 154 of 857 contaminants in the Substance Priority List . Toxicological studies have demonstrated that exposure to higher BD concentrations is associated with leukemia and cardiovascular disease and may raise the risks of reproductive illness, cancers, autism, and asthma in children. ,,− In 2019, the USEPA designated BD as a high-priority substance for risk evaluation under the Toxic Substances Control Act . To date, comprehensive information regarding the environmental fate of BD (e.g., persistence, degradation, and transformation), particularly under anoxic conditions, is largely lacking.…”

“…Uncontrolled emission, improper disposal, and accidental spillage have caused the detection of BD in soil, groundwater, surface water, and drinking water supplies, 3 which pose detrimental effects threatening human health. 1 BD has been identified in 17 of the 1867 U.S. Environmental Protection Agency (USEPA) National Priorities List (NPL) sites and is ranked 154 of 857 contaminants in the Substance Priority List. 4 Toxicological studies have demonstrated that exposure to higher BD concentrations is associated with leukemia and cardiovascular disease and may raise the risks of reproductive illness, cancers, autism, and asthma in children.…”

Diepoxybutane induces the p53‐dependent transactivation of the CCL4 gene that mediates apoptosis in exposed human lymphoblasts

“…Diepoxybutane (DEB) is the most toxic active metabolite of the environmental chemical 1,3‐butadiene (BD). [ 1 ] BD is a large production volume chemical that is regulated as a hazardous air pollutant. [ 2 ] Human exposure to this compound occurs in occupational settings, and in situations involving fires, automobile exhaust, and cigarette smoke.…”

“…[ 2 ] Human exposure to this compound occurs in occupational settings, and in situations involving fires, automobile exhaust, and cigarette smoke. [ 1,3 ] BD is a known mutagen, carcinogen, genotoxin, and teratogen, and its toxic effects are mediated primarily through its three epoxide metabolites, with DEB being the most potent. [ 1,4–7 ] DEB induces oxidative stress, DNA lesions, protein crosslinks, intra‐strand and interstrand DNA–DNA crosslinks, and apoptosis.…”