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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5
0.29 ppm (0.1-1 mg/m3) and also has been detected in the International Space Station atmosphere at about 0.5 mg/m3. The odor threshold for DCM in air is 250 ppm.
BACKGROUND AND SUMMARY OF ORIGINAL APPROACH
Studies in human volunteers show that DCM is well absorbed (up to 70%) by resting subjects during inhalation exposures, and exercise changes the absorption (DiVincenzo et al. 1972, Astrand et al. 1975, DiVincenzo and Kaplan 1981). Animal studies indicate that inhaled DCM is distributed in the liver, kidneys, lungs, brain, muscle, adipose tissues, and adrenals about 1 h after inhalation exposure, with the highest concentrations found in white adipose tissue and the next highest in liver (McKenna et al. 1982).
Systemically absorbed DCM is metabolized by two pathways. One pathway is via the microsomal mixed function oxidase (MFO) in the cytochrome P-450 system (cytochrome P-450 2E1 or CYP 2E1) (Gargas et al. 1986, Guengerich et al. 1991). The oxidative dehalogenation yields hydrogen chloride, carbon monoxide (CO), and carbon dioxide, with formyl chloride as an intermediate. At low exposures, this pathway predominates, and it is saturable at about 300 to 500 ppm (Gargas et al. 1986). The CO from this pathway binds reversibly to hemoglobin, forming carboxyhemoglobin (COHb). COHb reduces the oxygen-carrying capacity of the blood and also impairs the release of O2 from oxyhemoglobin, thus leading to tissue oxygen deficiency. In six sedentary human subjects exposed to DCM at 50, 100, 150, or 200 ppm for 7.5 h on 5 consecutive days, concentrations of COHb in blood were 1.9%, 3.4%, 5.3%, and 6.8%, respectively (DiVincenzo and Kaplan 1981). Numerous investigations have shown that CO is toxic to the cardiovascular system (changes heart rate and minute volume) and also to the central nervous system (CNS), where it has adverse effects such as impairing vigilance and performance in addition to causing headache, decreased vision, and other symptoms.
The second pathway is the glutathione (GSH)-dependent cytosolic pathway via glutathione S-transferase theta 1 (GSTT1) (Kubic and Anders 1975, Ahmed and Anders 1976, Andersen et al. 1987, Reitz et al. 1989). This pathway is a low-affinity first-order pathway that metabolizes DCM to hydrogen chloride, formaldehyde, and carbon dioxide. In the GSTT1 pathway, the haloalkane is metabolized to produce the reactive S-chloromethylglutathione intermediate, which has the capacity to interact with cellular DNA. The chloromethyl glutathione is short-lived; it undergoes rapid hydrolysis to yield formaldehyde. This GSH pathway is not saturable and is linear up to 10,000 ppm (Gargas et al. 1986). Carcinogenicity of DCM in long-term inhalation exposure of rodents has been attributed to metabolism of the compound via the GST-dependent pathway. Andersen et al. (1987) reported that large quantities of GSH-DCM conjugates in vivo may increase the frequency of lung and liver tumors that develop in some species of animals (such as B6C3F1 mice). DCM metabolism via the GSH