Chemical-Induced Atrial Thrombosis in NTP Rodent Studies—Supplementary Data

Abstract

Figure 1 presents the chemical names and structures of these 13 compounds. We summarize below the information concerning usages and effects in humans of these chemicals. Table 1 shows data from rats indicating the relationship between the severity of myocardial lesions and atrial thrombosis which were induced by bis(2-chloroethoxy)methane. Bis(2-chloroethoxy)methane (CEM): The majority is used for the production of polysulfide polymers, which are used in a variety of sealant applications because of their resistance to high temperatures and solvent degradation. No specific data for human toxicity are available, except those implicating it as an irritant of the skin and eye (NTP, 2003a, 2003b). 2-Butoxyethanol (2-BE): This substance is used extensively as a solvent in surface coatings, such as lacquers, enamels, varnishes, and latex paint; paint thinners and paint stripping formulations; inks; and degreasers and industrial and household cleaners. In humans, the chemical can induce hemolytic anemia and hemoglobinurea (ATSDR, 1998; Burkhart and Donovan, 1998; Gualtieri et al., 2003; NTP, 1998a). Only a few human cases involving hypotension, ventricular tachycardia, and/or arrhythmia exhibited cardiovascular effects (ATSDR, 1998; Gualtieri et al., 2003). C.I. Acid Red 114 (Red 114): This chemical is a benzidine congener-based dye, used to color textiles, paper, plastic, rubber, and leather. No epidemiological studies or reports of human health effects related to exposure to this chemical were found in the literature (NTP, 1991). C.I. Direct Blue 15 (Blue 15): A benzidine congener-based dye, this chemical is used as a dye to color textiles, paper, plastic, rubber, and leather. No epidemiological studies or reports of adverse health effects in humans related to exposure to this chemical were discovered in the literature (NTP, 1992a). C. I. Pigment Red 23 (Red 23): This chemical, a bluish-red dye used as a coloring agent in paints, inks, rubber, plastics, lacquers, and papers, is considered a genotoxic compound (Moller, 2000). No epidemiological studies or reports of human health effects related to exposure were found in the literature (NTP, 1992b). Diazoaminobenzene (DAB): Used as an intermediate, complexing agent and polymer additive, this chemical also occurs as an impurity in certain color additives used in cosmetics, food products, and pharmaceuticals. No information related to the toxicity of this compound in humans was found in a review of the available literature (NTP, 2002b). Diethanolamine (DEL): This compound is widely used in the preparation of diethanolamides and diethanolamine salts that are formulated into soaps and surfactants used in liquid laundry and dishwashing detergents, cosmetics, shampoos, and hair conditioners. No references to human side effects caused by this chemical were found in a review of the literature (NTP, 1992c, 1999). 3,3′-Dimethoxybenzidine dihydrochloride: Used principally as an intermediate in the production of commercial bisazobiphenyl dyes, this compound is used to color textiles, paper, plastic, rubber, and leather. No epidemiological studies or reports of effects, especially hematological, upon human health related to exposure were discovered in the literature (NTP, 1990). Hexachloroethane (HCE): This chemical is used in organic synthesis as a retarding agent in fermentation and camphor substitute in nitrocellulose, in pyrotechnics and smoke devices, in explosives, and as a solvent. No epidemiological studies or reports of human health effects, including cardiovascular, related to exposure were found in the literature (ATSDR, 1997; NTP, 1989, 2002a). Isobutene (IBT): This compound, which has been detected in the urban atmosphere, is used primarily to produce diisobutylene, trimers of butyl rubber, and other polymers. During halothane anesthesia, a 10-fold increase over normal occurs in the concentration of isobutene in the breath of patients; the source was speculated to be terpenes or ubiquinones (Hempel et al., 1980). No epidemiological studies or reports of human health effects related to exposure were discovered in the literature (NTP, 1998b). Methyleugenol (MEG): The chemical acts as a flavoring agent in jellies, baked goods, nonalcoholic beverages, chewing gum, candy, pudding, relish, and ice cream and is also