Acetaldehyde exposure

Lam, C.-W., Casanova, M. Heck, H.D A. (1986) Decreased extractability of DNA from proteins in the rat nasal mucosa after acetaldehyde exposure. Fundam. appl. Toxicol., 6, 541— 550... 

Acetaldehyde exposure presented a chronic health risk and a concern for cancer risk with (lifetime) risk estimates of 10-4 based on potency estimates. 

In 1921, 33 years after Klinger s discovery, Dimroth and Hilcken reported a similar transformation of quinizarinquinone (8) with acetaldehyde. Exposure to direct sunlight for 12 days gave the corresponding monoester 9 in 49% yield (Scheme 4). However, when they repeated the experiment during the less light intensive autumn season over an extended period of 1.5 months, they obtained a mixture of quinizarin (the reduction product of 8) and the monoester 9. 

Interest ia the toxicity of aldehydes has focused primarily on specific compounds, particularly formaldehyde, acetaldehyde, and acroleia (13). Litde evidence exists to suggest that occupational levels of exposure to aldehydes would result ia mutations, although some aldehydes are clearly mutagenic ia some test systems. There are, however, acute effects of aldehydes. 

Anesthesia. Materials that have unquestionable anesthetic properties are chloral hydrate [302-17-0] paraldehyde, dimethoxymethane [109-87-5] and acetaldehyde diethyl acetal. In iadustrial exposures, however, any action as an anesthesia is overshadowed by effects as a primary irritant, which prevent voluntary inhalation of any significant quantities. The small quantities which can be tolerated by inhalation are usually metabolized so rapidly that no anesthetic symptoms occur. 

Exposure of the ethylidene diacetate to an aromatic sulphonic acid in the presence of five times its weight of acetic anhydride as diluent at 136°C will yield the following mixture 40% vinyl acetate 28% acetic acid 20% acetic anhydride 4% ethylidene diacetate 8% acetaldehyde. 

A model developed by Leksawasdi et al. [11,12] for the enzymatic production of PAC (P) from benzaldehyde (B) and pyruvate (A) in an aqueous phase system is based on equations given in Figure 2. The model also includes the production of by-products acetaldehyde (Q) and acetoin (R). The rate of deactivation of PDC (E) was shown to exhibit a first order dependency on benzaldehyde concentration and exposure time as well as an initial time lag [8]. Following detailed kinetic studies, the model including the equation for enzyme deactivation was shown to provide acceptable fitting of the kinetic data for the ranges 50-150 mM benzaldehyde, 60-180 mM pyruvate and 1.1-3.4 U mf PDC carboligase activity [10]. 

The retention of 1,2-dibromoethane in tissues and body fluids can be altered by concurrent exposure to modifiers of enzyme activity, such as disulfiram (Plotnick et al. 1979). The concentration of radiolabeled 1,2-dibromoethane in the liver, kidneys, spleen, testes, and brain increased significantly in rats fed disulfiram in the diet for 12 days before an oral dose of 15 mg C-1,2- dibromoethane/kg compared with rats not fed disulfiram. Disulfiram, an inhibitor of P-450 metabolism (via action on acetaldehyde dehydrogenase), was found to increase the uptake of C into liver nuclei. These observations correlate well with the results of chronic studies (Wong et al. 1982) that demonstrated enhanced tumorigenic effects in the liver and testes following combined 1,2-dibromoethane and disulfiram exposure. 

Ethylene and D2O were formed only above a threshold exposure of the surface to ethanol. Figure 27 shows that acetaldehyde was first formed this was the result of the reactions... 

In several smdies, parenteral exposure of pregnant rats and mice has produced embry-otoxic, fetotoxic, and teratogenic effects however, maternal toxicity was not adequately evaluated, and the selective developmental effects of acetaldehyde cannot be evaluated."... 

Kruysse A, Eeron VJ, Til EIP Repeated exposure to acetaldehyde vapor. Studies in Syrian golden hamsters. Arch Environ Health 30 449-152, 1975... 

Woutersen RA, Eeron VJ Inhalation toxicity of acetaldehyde in rats. IV. Progression and regression of nasal lesions after discontinuation of exposure. Toxicology 47 295-305, 1987... 

Most of the alcohol distributes into body water, but like most solvents and anesthetics some distributes into fat. It is excreted in the urine and breath, hence the utility of taking breath samples to evaluate alcohol exposure. The majority of alcohol is metabolized in the liver. Alcohol dehydrogenase (ADH) metabolizes alcohol to acetaldehyde. Acetaldehyde is toxic, with elevated levels causing flushing, headache, nausea, and vomiting. Acetaldehyde is in turn quickly metabolized to the less toxic acetate by acetaldehyde dehydrogenase (ALDH) (Figure 3.1). 

In the late 1950s the subtle and serious consequences of methyl mercury exposure became evident in Minamata, Japan. Initially, early signs of uncoordinated movement and numbness around the lips and extremities, followed by constriction in visual fields in fishermen and their families, baffled health experts. Developmental effects were clearly evident in infants who exhibited subtle to severe disabilities. This spectrum of adverse effects was finally related to methyl mercury exposure from consumption of contaminated fish. Minamata Bay was contaminated with mercury and methyl mercury from a factory manufacturing the chemical acetaldehyde. Mercury was used in the manufacturing process, which also resulted in both mercury and methyl mercury being discharged into Minamata Bay. The fish in the bay accu-... 

Oxidation is another important factor for the wine-aging process. Major oxidation reactions taking place in wine following oxygen exposure actually involve other wine constituents that are primarily ethanol and, in the presence of metal ions, tartaric acid rather than flavonoids, although phenolic compounds have been shown to participate in oxidation of ethanol to acetaldehyde. ... 

According to the 1981-83 National Occupational Exposure Survey (NOES, 1997), approximately 220 000 workers in the United States were potentially exposed to acetaldehyde (see General Remarks). Occupational exposure to acetaldehyde may occur in its production, in the production of acetic acid, acetate esters and other chemicals and in other applications. 

The American Conference of Governmental Industrial Hygienists (ACGIH) (1997) has not recommended an 8-h time-weighted average threshold limit value but has recommended 45 mg/ni as the ceiling value for occupational exposures to acetaldehyde in... 

In a survey of chemical plants (without prior hypothesis) in the German Democratic Republic, nine cancer cases were found in a factory where the main process was dimerization of acetaldehyde and where the main exposures were to acetaldol (3-hydroxybu-tanal), acetaldehyde, butyraldehyde, crotonaldehyde (IARC, 1995) and other higher, condensed aldehydes, as well as to traces of acrolein (lARC, 1985). Of the cancer cases, five were bronchial tumours and two were carcinomas of the oral cavity. All nine patients were smokers. The relative frequencies of these tumours were reported to be higher than those expected in the German Democratic Republic. [The Working Group noted the mixed exposure, the small number of cases and the poorly defined exposed population.]... 

Acetaldehyde was tested for carcinogenicity in rats by inhalation exposure and in hamsters by inhalation exposure and intratracheal instillation. Following inhalation exposure, an increased incidence of carcinomas was induced in the nasal mucosa of rats, and laryngeal carcinomas were induced in hamsters. In another inhalation study in hamsters, using a lower exposure level, and in an intratracheal instillation study, no increased incidence of tumours was observed. In hamsters, inhalation of acetaldehyde enhanced the incidence of respiratory-tract tumours produced by intratracheal instillation of benzo a -pyrene (lARC, 1985). 

The irritant effect of acetaldehyde vapour, which is reported to cause coughing and a burning sensation in the nose, throat and eyes, usually prevents exposure to a level sufficient to cause depression of the central nervous system. A splash of liquid acetaldehyde was reported to cause a burning sensation, lachrymation and blurred vision. Prolonged periods of contact with the skin result in erythema and bums repeated contact may result in dermatitis, due either to primary irritation or to sensitization. 

Exposure to acetaldehyde may occur in its production, and in the production of acetic acid and various other chemical agents. It is a metabolite of sugars and ethanol in humans and has been detected in plant extracts, tobacco smoke, engine exliaust, ambient and indoor air, and in water. 

Acetaldehyde is metabolized to acetic acid. During inhalation exposure of rats, degeneration of nasal epithelium occurs and leads to hyperplasia and proliferation. 

Lundgren et al. (1999) evaluated the field exposures of painters to a low-VOC and a conventional water-based paints in Sweden. They found that exposures to TVOC, 1,2-propylene glycol, acetaldehyde and ammonia were 3-12 times lower for the low-VOC paint, but exposure to formaldehyde (160-180 pgm ) was 3-4 times higher. Brown (2000) reported that emissions from four Australian VOC-free paints included typical aromatic VOCs, dibutyl ether, ethylene glycol butyl ether, diethylene glycol butyl ether and Texanol , though at order of magnitude reduced levels c.f. conventional water-based paints, as well as formaldehyde and benzaldehyde. 

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