Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants Volume 2 (1996) / Chapter Skim
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B8 Methylene Chloride
B8 Methylene Chloride
Pages 277-306
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From page 277... ...
There is no known use of methylene chloride in spacecraft, but methylene chloride has been shown to off-gas in space shuttles reaching typically 0.1 ppm in a few days (NASA, 19891.
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From page 278... ...
showed that the methyTene chloride concentration in venous blood reached a plateau in 2 h during a 7.5-h exposure of four to six sedentary human volunteers to methylene chloride at 50-150 ppm. However, when exposed to methylene chloride at 200 ppm, the blood concentration failed to clateau in 7.5 h (DiVincenzo and Kaplan, 19811.
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From page 279... ...
Excretion DiVincenzo and Kaplan (1981) reported that, after a 7.5-h methylene chloride exposure at 50-200 ppm in four to six human subjects, less than 5 % of the absorbed methylene chloride was excreted unchanged in the expired air, and 25-34% was excreted as carbon monoxide during
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From page 280... ...
This suggests that, after the 1-2 h exposure, methylene chloride is released from some of the tissues and metabolized into carbon monoxide, leading to a temporary accumulation of COHb in blood. It is interesting that such a phenomenon does not occur in longer methylene chloride exposures.
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From page 281... ...
In the same study, these CNS effects were reproduced by a carbon monoxide exposure that yielded 5 % COHb. Acute methylene chloride exposures could impair vigilance performance in humans.
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From page 282... ...
A 6-h exposure at 5000 ppm or higher increases the hepatic triglyceride concentration in guinea pigs (Balmer et al., 1976~. Subchronic and Chronic Toxicity Subchronic exposures to methylene chloride have been reported to produce COHb and toxic effects in the liver, kidney, and the respiratory system.
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From page 283... ...
(1972) detected fatty changes and cytoplasmic vacuolization in the liver, as well as nonspecific tubular degeneration and regeneration in the kidney.
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Mice in both the 2000- and 4000-ppm groups developed only cytological degeneration in the liver. Tn comparison, several types of hepatic pathology were found in the 1000-, 2000-, and 4000-ppm groups: focal granulomatous inflammation, focal necrosis, hemosiderosis, and cytoplasmic vacuolization.
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From page 285... ...
In male rats, however, chronic methylene chloride exposures led to giomerulonephropathy at 1500 and 3500 ppm. in terms of liver injuries, chronic methylene chloride exposures at 500, 1500, or 3500 ppm produced vacuolization consistent with fatty liver in both male and female rats and they also caused multinucleared hepatocytes in female rats.
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From page 286... ...
In the NTP's chronic toxicity study (1986) , methylene chloride produced leukemia and benign mammary tumors in female rats and alveolar and bronchiolar adenomas and carcinomas in mice, as well as hepatocellular adenomas and carcinomas in mice.
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From page 287... ...
exposed five female rats to methylene chloride at 4500 ppm, 6 in/d, 7 d/w, for 12-14 ~ before breeding and on days 1-17 of gestation. Hardin and Manson did not detect any increases in the incidence of skeletal or soft-tissue malformations or external anomalies.
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288 Cal ._ .o o no at; Cal U
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From page 292... ...
The lowest AC among the three end points will be chosen as the SMAC for each exposure duration. CNS Depression As discussed in the Toxicity Summary, one of the major acute effects of methylene chloride is CNS depression, which appears to be due to carbon monoxide formed from methylene chloride's metabolism.
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From page 293... ...
To calculate the acceptable 7-d, 30-d, and 180-d methylene chloride concentrations based on the carbon monoxide metabolite, the target COHb concentrations of 1.6% were adopted from the 7-d, 30-d, and 180-d carbon monoxide SMACs. According to the PB-PK model of Andersen et al.
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From page 294... ...
1972 , Concentration x Time. it should be noted that the National Research Council's Subcommittee on SMACs recognized the potential that methylene chIoride's toxicity due to COHb formation could be aggravated by a reduction in the mass of red blood cells (RBCs)
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From page 295... ...
showed that liver histopathology became somewhat more severe as the exposure was lengthened, but the hepatic triglyceride concentration did not increase linearly with the exposure duration. Their results are summarized in Table 8-6.
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The NTP (1986) study also showed that exposures to rats at 1000, 2000, or 4000 ppm, 6 in/d, 5 d/w, for 2 y could lead to cytoplasmic vacuolization, hemosiderosis, and focal granulomatous inflammation in liver.
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From page 297... ...
instead of using the airborne methylene chloride concentrations to calculate the i0-4 tumor dose, it is better to use the doses of active metabolite produced by the glutathione transferase pathway in the lung and liver, as estimated by a physiologically based pharmacokinetic mode! (Andersen et al., 1987~.
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From page 298... ...
7-d exposure level that would produce a 10-4 excess tumor risk = 1.1 ppm x 3728 = 4100 ppm. With a similar approach, 871 and 146.7 are calculated to be the adjustment factors for converting a lifetime exposure concentration to 30-d and 180-d exposure concentrations for the same excess tumor risk (NRC, 1992~.
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From page 299... ...
No adjustments of the SMACs are needed for any microgravity-induced physiological changes. The reason is that the in-flight hemoglobin concentrations obtained in Skylabs were higher than the preflight values by only 10%, so the carbon monoxide produced from methylene chloride metabolism is not going to be significantly more toxic in-flight than on earth.
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300 v, o ~ At o At At ¢ cd v)
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1991. Physiologically based pharmcokinetic modeling with dichIoromethane, its metabolite, carbon monoxide, and blood carboxyhemogIobin in rats and humans.
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1972. Human and canine exposure to methylene chloride vapor.
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1978. Toxicological studies on dichIoromethane, a solvent simulating carbon monoxide poisoning.
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1 974. In vivo conversion of methylene chloride to carbon monoxide.
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From page 305... ...
1990. Carbon monoxide.
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