Exposure of members of the general public to methylene chloride /i.e., dichloromethane/ will occur from its use in consumer products such as paint removers, which can result in relatively high levels being found in indoor air. Occupational exposure during production arises primarily during filling and packaging (manufacturing is in closed systems). Because of its use in paint strippers, occupational exposure to methylene chloride occurs during formulation of paint remover, original equipment manufacturer, and in commercial furniture refinishing. Methylene chloride is widely used as a process solvent in the manufacture of a variety of products ... Biological monitoring of methylene chloride exposure can be based on measurement of the solvent itself in exhaled air or blood. However, as production of carbon monoxide with exposure for more than 3-4 hr/day appears to be the limiting factor in regard to health risk, biological monitoring based upon either analysis of carbon monoxide in exhaled air or of carboxyhemoglobin in blood is to be preferred. ... Methylene chloride is rapidly absorbed through the alveoli of the lungs into the systemic circulation. It is also absorbed from the gastrointestinal tract, and dermal exposure results in absorption but at a slower rate than via the other routes of exposure. Methylene chloride is quite rapidly excreted, mostly via the lungs in the exhaled air. It can cross the blood-brain barrier and be transferred across the placenta, and small amounts can be excreted in urine or in milk. At high concentrations, most of the absorbed methylene chloride is exhaled unchanged. The remainder is metabolized to carbon monoxide, carbon dioxide, and inorganic chloride. ... One pathway involves oxidative metabolism mediated by cytochrome P-450 and leads to both carbon monoxide and carbon dioxide. This pathway appears to operate similarly in all rodents studied and in man. ... The other pathway involves a glutathione transferase and leads via formaldehyde and formate to carbon dioxide. This route seems only to become important at doses above the saturation level of the "preferred" oxidative pathway ... /in/ man it seems to be used very little at any dose. Species difference in glutathione transferase metabolism correlates well with the observed species diffence in carcinogenicity. ... In the aquatic environment, fish and amphibian embryos have been shown to be the most sensitive ... The acute toxicity of methylene chloride /on laboratory mammals/ by inhalation and oral administration is low. ... Acute effects after methylene chloride administration by various routes of exposure are primarily associated with the central nervous system (CNS), and the liver, and these occurred at high doses. ... Occasionally other organs were affected such as the kidney or respiratory system. ... Cardiac sensitization to adrenaline-induced arrhythmia have been reported. ... Prolonged exposure to high concentrations of methylene chloride caused reversible CNS effects, slight eye irritation and mortality in several laboratory species. Body weight reduction was observed in rats ... and in mice .... Slight effects on the liver were noted in dogs ... Other target organs are the lungs and the kidneys. ... Methylene chloride is moderately irritant to the skin and eyes of experimental animals. Methylene chloride is not teratogenic in rats or mice ... Within the limitations of the short-term tests currently available there is no conclusive evidence that methylene chloride is genotoxic in vivo. ... Methylene chloride is carcinogenic in the mouse, causing both lungs and liver tumors, following exposure to high concentrations ... Syrian hamsters exposed to methylene chloride by inhalation ... showed no evidence of a carcinogenic effect ... Rats exposed to methylene chloride via various routes have shown increased incidences of tumors at certain sites. ... The mechanism by which methylene chloride induces mammary adenomas in the rat is important for human hazard assessment. ... It seems most likely ... that the increased incidence of mammary adenomas is the result of an indirect mechanism operating via hyperprolactinemia. In humans, there is conflicting evidence on whether mammary tumors are responsive to prolactin as is the case in the rat. ... Prolactin is not luteotrophic in primates. It is unlikely, therefore, that this mechanism of tumor development is of relevance to man. ... / In humans/ Methylene chloride irritates the skin and eyes, especially when evaporation is prevented. In these circumstances, prolonged contact may cause chemical burns. ... Fatalities due to accidental inhalation and skin contamination have been reported. The main toxic effects of methylene chloride are reversible CNS depression and /carboxyhemoglobin/ formation. Liver and renal dysfunctions and effects of hematological parameters have also been reported ... Neurophysiological and neurobehavorial disturbances have been observed in human volunteers ... An increased rate of spontaneous abortion ... has been attributed to exposure to methylene chloride. A causal relationship was not established because of insufficiencies in the design of the study. Several mortality studies in relevant cohorts show an inconsistent pattern in the causes of death. ...[Environmental Health Criteria 164: Methylene Chloride (Second Edition). pp. 21-29 (1996) by the International Programme on Chemical Safety (IPCS) under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation and the World Health Organization.] **QC REVIEWED**
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