1,3-Butadiene carcinogenicity

Some analysts, such as US EPA (2002) for the analysis of 1,3-butadiene carcinogenicity examined in more detail below, assumed a distribution shape (normal in that case, with a standard deviation calculated from the estimated MLE and confidence limits of the qi estimates). However, as will be shown below, such assumptions are approximate at best even in favorable cases. Zeise et al. (1991) demonstrated a procedure to generate the required distribution by tracing the likelihood profile of the linear term ( i) for a linearized multistage fit to dichotomous tumor data. This used a modified version (Zeise and Salmon 1991) of the MSTAGE program developed by Crouch (1985). More recently. Crouch (2006) developed a similar program that provides the likelihood distribution for estimates of qi when... 

Mechanistic studies conducted in whole animals and in rodent and human tissues using biochemical and molecular biological approaches have provided important insights into the likely critical steps in the initiation of butadiene carcinogenicity and the identity of the most likely chemical species responsible for the development of tumours. 

Outside of carbon monoxide for which the toxicity is already well-known, five types of organic chemical compounds capable of being emitted by vehicles will be the focus of our particular attention these are benzene, 1-3 butadiene, formaldehyde, acetaldehyde and polynuclear aromatic hydrocarbons, PNA, taken as a whole. Among the latter, two, like benzo [a] pyrene, are viewed as carcinogens. Benzene is considered here not as a motor fuel component emitted by evaporation, but because of its presence in exhaust gas (see Figure 5.25). 

Exposure studies have been made using mice and rats (257). These experiments have demonstrated species differences in butadiene toxicity and carcinogenicity. Butadiene was found to be a potent carcinogen in the mouse, but only a weak carcinogen in the rat. The interpretations have focused on differences in toxification rates and detoxification metaboHsms as causative factors (257). The metaboHsm is beHeved to proceed through intermediates involving butadiene monoepoxide and butadiene diepoxide (257). A similar mechanism has been proposed for its biodegradation pathway (258). 

Compounds considered carcinogenic that may be present in air emissions include benzene, butadiene, 1,2-dichloroethane, and vinyl chloride. A typical naphtha cracker at a petrochemical complex may release annually about 2,500 metric tons of alkenes, such as propylenes and ethylene, in producing 500,000 metric tons of ethylene. Boilers, process heaters, flares, and other process equipment (which in some cases may include catalyst regenerators) are responsible for the emission of PM (particulate matter), carbon monoxide, nitrogen oxides (200 tpy), based on 500,000 tpy of ethylene capacity, and sulfur oxides (600 tpy). 

Chromium, (ri6-benzene)tricarbonyl-stereochemistry nomenclature, 1,131 Chromium complexes, 3,699-948 acetylacetone complex formation, 2,386 exchange reactions, 2,380 amidines, 2,276 bridging ligands, 2,198 chelating ligands, 2,203 anionic oxo halides, 3,944 applications, 6,1014 azo dyes, 6,41 biological effects, 3,947 carbamic acid, 2,450 paddlewheel structure, 2, 451 carboxylic acids, 2,438 trinuclear, 2, 441 carcinogenicity, 3, 947 corroles, 2, 874 crystal structures, 3, 702 cyanides, 3, 703 1,4-diaza-1,3-butadiene, 2,209 1,3-diketones... 

IARC. 1979. Acrylonitrile, acrylic and modacrylic fibres, and acrylonitrile-butadiene-styrene and styrene-acrylonitrile copolymers. IARC monographs on the evaluation of the carcinogenic risk of... 

Buta-1,3-diene (10.101, Fig. 10.24) is a gaseous chemical used heavily in the rubber and plastics industry, the presence of which in the atmosphere is also a concern. Butadiene is suspected of increasing the risks of hematopoietic cancers, and it is classified as a probable human carcinogen. Butadiene must undergo metabolic activation to become toxic the metabolites butadiene monoepoxide (10.102, a chiral compound) and diepoxybutane (10.103, which exists in two enantiomeric and one meso-form) react with nucleic acids and glutathione [160 - 163], as does a further metabolite, 3,4-epoxybutane-l,2-diol (10.105). Interestingly, butadiene monoepoxide is at least tenfold more reactive than diepoxybutane toward nucleic acids or H20. Conjugation between the C=C bond and the oxirane may account for this enhanced reactivity. 

A. A. Elfarra, R. J. Krause, R. R. Selzer, Biochemistry of 1,3-Butadiene Metabolism and Its Relevance to 1,3-Butadiene-Induced Carcinogenicity , Toxicology 1996, 113, 23 - 30 R. A. Kemper, R. J. Krause, A. A. Elfarra, Metabolism of Butadiene Monoxide by Freshly Isolated Hepatocytes from Mice and Rats Different Partitioning between Oxidative, Hydrolytic, and Conjugations Pathways , Drug Metab. Dispos. 2001, 29, 830 - 836. 

Styrene is a commercially important monomer that is used extensively in the manufacture of polystyrene resins and in co-polymers with acrylonitrile and 1,3-butadiene (reinforced plastics). Exposure to styrene occurs due to intake of food that has been in contact with styrene-containing polymers. lARC has determined that styrene is possibly carcinogenic to humans. There is no restriction on using styrene within the European Union (i.e., there is no SML). 

Toxicology. 1,3-Butadiene is an irritant of the eyes and mucous membranes at extremely high concentration it causes narcosis in animals, and severe exposure is expected to produce the same effect in humans. It is carcinogenic in experimental animals and is considered a probable human carcinogen. 

Toxicological studies have shown butadiene to be a multisite animal carcinogen with marked differences in potency across rodent species." ... 

The 2003 ACGIH threshold limit valuetime-weighted average (TLV-TWA) for butadiene is 2 ppm (4.4mg/m ) with an A2-suspected human carcinogen designation. 

Huff JE, Melnick RL, Solleveld HA, et al Multiple organ carcinogenicity of 1,3-butadiene in B6C3F1 mice after 60 weeks of inhalation exposure. Science 227 548-549, 1985... 

Inhalation toxicity studies with 1,3-butadiene two-year toxicity/carcinogenicity study in rats. Am Ind Hyg Assoc f 48 407-413, 1987... 

Butadiene is a colorless, odorless, flammable gas, with a bp of -4.7°C. As of 2000 butadiene has been on the Known to Be a Human Carcinogen list of the Department of Health and Human Services. It has a time-weighted average threshold limit value (TLV) of 2 ppm. TLVs and carcinogens will be discussed more fully under benzene. Butadiene is expensive to store because it polymerizes easily and must be refrigerated. 

Benzene is a clear, colorless, flammable liquid with a pleasant characteristic odor, bp 80.1°C, flash point -11.1°C, and ignition temperature 538°C. Benzene has been found to be very toxic and is on the list of Known to Be Human Carcinogens published every two years by the Department of Health and Human Services under the National Toxicology Program (NTP). There are four top 50 chemicals on this worst carcinogen list benzene 1,3-butadiene ethylene oxide and vinyl chloride. There are also four chemicals in the top 50 on the Reasonably Anticipated to Be Human Carcinogens list acrylonitrile, ethylene dichloride, formaldehyde, and propylene oxide. 

U.S. price trends show that cotton and polyester are the most popular for good reason they are the cheapest. Nylon and acrylic have had price increases over the last few years, part of which may be due to improvements and safeguards needed to manufacture their precursors acrylonitrile, butadiene, and benzene, which are on carcinogen lists. 

As discussed in detail in Chapters 6 and 16, organic compounds play a key role in the formation of ozone, particles, and other species of interest. While some of the individual species are of concern from the point of view of health effects (e.g., the carcinogens benzene and 1,3-butadiene), for most VOC it is because of their... 

Butadiene, a major commodity chemical used in the production of synthetic rubber, is listed as one of 189 hazardous air pollutants under the 1990 Clean Air Act Amendments. Butadiene is a carcinogen in rats and mice, with mice being substantially more sensitive than rats. The extent to which butadiene poses risk of cancer to humans exposed to this chemical is uncertain. The data include in vitro studies on butadiene metabolism using tissues from humans, rats, and mice as well as experimental data and physiological model predictions for butadiene in blood and butadiene epoxides in blood, lung, and liver after exposure of rats and mice to inhaled butadiene (Bond et al., 1996). 

Overall, our analyses have shown that HERP values for some historically high exposures in the workplace—to butadiene and tetrachloroethylene—and to some pharmaceuticals—clolibrate —rank high, and that there is an enormous background of naturally occurring rodent carcinogens in typical portions of common foods. The background of natural exposures casts doubt on the relative importance of low-dose exposures to residues of synthetic chemicals such as pesticides. (A committee of the National Research Council of the National Academy of Sciences reached similar conclusions about natural vs. synthetic chemicals in the diet, and called for further research on natural chemicals.) 16... 

An example of this type of a safer chemical is methacrylonitrile (1) compared with acrylonitrile (2) (Figure 1.1). Both compounds are a, 3-unsaturated aliphatic nitriles, and structurally very similar, but 2 causes cancer whereas 1 does not appear to do so. Among other applications, 2 is used in the production of acrylic and modacrylic fibers, elastomers, acrylonitrile-butadiene-styrene and styrene-acrylonitrile resins, nitrile rubbers, and gas barrier resins. In a study conducted by the US National Toxicology Program (NTP) in which 2 was administered orally to mice for 2 years, there was clear evidence that it caused cancer in the treated mice (in addition to causing other toxic effects), and is classified by the NTP as a probable human carcinogen [26]. 

Butadiene was tested for carcinogenicity by inhalation exposure in four experiments in mice and one experiment in rats. 

The initial metabolite of 1,3-butadiene, 1,2-epoxy-3-butene, yielded equivocal results in carcinogenicity tests, whereas the subsequent metabolite, l,2 3,4-diepoxybutane, was carcinogenic to mice and rats when administered by skin application or by subcutaneous injection. 

There is limited evidence in humans for the carcinogenicity of 1,3-butadiene. 

Bucher, J.R., Melnick, R.L. Hildebrandt, P.K. (1993) Lack of carcinogenicity in mice exposed once to Irigh concentrations of 1,3-butadiene. J. natl Cancer Inst., 85, 1866-1867... 

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